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Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has alarmingly increased in incidence in recent decades. One of the most serious complications of T2DM is diabetic cardiomyopathy (DCM), an often underrecognized yet severe condition that is a leading cause of mortality among diabetic patients. In the early stages of DCM, patients typically show no symptoms and maintain normal systolic and diastolic left ventricle function, making early detection challenging. Currently available clinical markers are often not specific enough to detect the early stage of DCM. Conventional biomarkers of cardiac mechanical stress and injury, such as natriuretic peptides (NPs) and cardiac troponin I (cTnI), have shown limited predictive value for patients with T2DM. NPs have proven efficacy in detecting diastolic dysfunction in diabetic patients when used alongside 2D echocardiography, but their utility as biomarkers is limited to symptomatic individuals. While cTnI is a reliable indicator of general cardiac damage, it is not specific to cardiac injury caused by high glucose levels or T2DM. This underscores the need for research into biomarkers that can enable early diagnosis and management of DCM to reduce mortality rates. Promising novel biomarkers that showed good performance in detecting diastolic dysfunction or heart failure in diabetic patients include galectin-3, ST2, FGF-21, IGFBP-7, GDF-15, and TGF-β. This review summarizes the current understanding of DCM biomarkers, aiming to generate new ideas for the early recognition and treatment of DCM by exploring related pathophysiological mechanisms.

Background : The pathogenesis of MASLD (metabolic dysfunction-associated steatotic liver disease) is driven by environmental, genetic, metabolic, immune, and inflammatory factors. IL-17 and TLR4 determine hepatic steatosis, inflammation, and finally fibrosis. Objectives : To explore the associations between the plasma levels of inflammatory markers, TLR4, and the cytokines IL17A/F, as well as their connections with the degree of hepatic steatosis and the risk of hepatic fibrosis (defined by the FIB-4 score) in MASLD patients. Methods : The study cohort included 80 patients diagnosed with MASLD. The IL-17A/F and TLR4 serum concentrations were determined using the ELISA method. Results : We found a significant difference in the CAR levels (C-reactive protein to albumin ratio) when comparing MASLD patients with severe steatosis to those with mild/moderate steatosis (Student's t test, t (71) = 2.32, p = 0.023). The PIV (pan-immune inflammatory value) was positively correlated with the SII (systemic immune inflammation index), (r = 0.86, p < 0.0001) and the CAR (r = 0.41, p = 0.033) in MASLD patients with severe steatosis. In contrast, increased values of the LMR (lymphocyte to monocyte ratio) were significantly associated, with decreased levels of the SII (ρ = -0.38, p = 0.045). We also found a positive correlation between the CAR and the SII (r = 0.41, p = 0.028). In patients with mild/moderate steatosis, a significant positive correlation was observed between the SII and IL17A (r = 0.36, p = 0.010), the PIV and the CAR (r = 0.29, p = 0.011), the PIV and the SII (r = 0.87, p < 0.0001) and the PIV and IL17A (r = 0.3, p = 0.036). A negative correlation was observed between the LMR and the SII (r = -0.55, p < 0.0001) and the CAR and IL17F (r = -0.37, p = 0.011). Regarding the inflammatory markers, the PIV (336.4 vs. 228.63, p = 0.0107), and the SII (438.47 vs. 585.39, p = 0.0238) had significantly lower levels in patients with an intermediate-high risk of hepatic fibrosis as compared with the patients with a low risk of hepatic fibrosis. The PNI (prognostic nutritional index) (47.16 vs. 42.41, p = 0.0392) had significantly different levels in patients with the likelihood of hepatic fibrosis than those with a low risk of hepatic fibrosis. Conclusions : Regarding the inflammatory markers, the PIV and the SII hold promise as biomarkers for discriminating between MASLD patients with an intermediate-high risk and those with a low risk of hepatic fibrosis. Our findings underscore the role of IL-17A and its potential relationship with inflammatory markers in MASLD pathogenesis and the progression to hepatic fibrosis.

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA-metal complex interactions (including some representative examples) and on presenting the methods currently used to study them.

Burnout among healthcare workers has been extensively studied since its initial recognition in 1960, with its defining characteristics established by Maslach in 1982. The syndrome, characterized by emotional exhaustion, depersonalization, and low personal accomplishment, is exacerbated by work-related stress and has profound implications for individual and societal well-being., Methods: A review of the literature, including PubMed searches and analyses of risk factors and protective measures, was conducted to assess the prevalence, impacts, and biomarkers associated with burnout among healthcare workers. Various instruments for evaluating burnout were examined, including the widely used Maslach Burnout Inventory, alongside specific tools tailored to different occupational populations., Results: Healthcare workers, particularly physicians, exhibit significantly higher rates of burnout compared to the general population. Factors such as night shifts, workload, and exposure to biohazards contribute to elevated burnout risk. Biomarkers like cortisol, melatonin, and thyroid hormones have been linked to burnout, highlighting physiological implications., Conclusions: Burnout poses significant challenges to healthcare systems globally, impacting patient care, worker retention, and overall well-being. Identifying and addressing risk factors while promoting protective factors such as resilience and social support are crucial in mitigating burnout. Further research into prevention strategies and biomarker monitoring is warranted to support the mental and physical health of healthcare workers.

Background and Aims: Nonselective beta-blockers (NSBBs) can lower the risk of first decompensation in patients with cirrhosis and clinically significant portal hypertension (CSPH) (identified by a hepatic venous pressure gradient ≥10 mm Hg) with active etiology. Our aim was to examine the effect of NSBBs on first decompensation occurrence in patients with cirrhosis and enduring CSPH after etiological treatment., Methods: Patients with compensated cirrhosis and clinical evidence of CSPH (gastroesophageal varices [GEVs] and/or spontaneous portosystemic collaterals [SPSSs]) after 2 years from etiological treatment. The primary endpoint was first decompensation (occurrence of variceal bleeding, ascites, or hepatic encephalopathy) in patients on NSBBs vs off NSBBs., Results: The final cohort included 406 patients. Baseline characteristics of patients on NSBBs (n = 187) and off NSBBs (n = 219) were comparable, except for signs of portal hypertension that were more pronounced in the on-NSBB group. During a mean follow-up of 32 months, 127 (31%) patients decompensated, with ascites being the most common (77%) decompensating event. Decompensation rates were lower in patients on NSBBs (16% vs 44%; P < .0001). The benefit of NSBBs on decompensation was maintained in patients with small GEVs (17% vs 43%; P < .0001), in those with spontaneous portosystemic shunt only (8% vs 43%; P = .003), and in each different etiology, including hepatitis C virus-cured cirrhosis (9% vs 32%; P < .0001). At Cox regression analysis, hemoglobin, Child-Pugh, Model for End-Stage Liver Disease-Sodium, diabetes at baseline, and previous bacterial infections were independent predictors of decompensation, while NSBB use had a protective effect (hazard ratio, 0.32; 95% confidence interval, 0.20-0.49; P < .0001). NSBB use significantly reduced bacterial infection rates (hazard ratio, 0.36; 95% confidence interval, 0.22-0.58; P < .0001)., Conclusion: NSBBs decrease the risk of first decompensation in patients with cirrhosis and enduring CSPH after etiological treatment., (Copyright © 2024. Published by Elsevier Inc.)

(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case-control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development.

Vitamin D deficiency and type 2 diabetes mellitus are risk factors for colorectal cancer, suggesting a role for vitamin D receptor (VDR) and insulin receptor (INSR) gene polymorphisms. We investigated the prevalence of the VDR-BsmI (rs1544410) and NsiI A/G-INSR (rs2059806) polymorphisms and their associations with colorectal adenoma (CRA) in a Romanian population. A case-control study was conducted with 110 participants (67 with CRA and 43 controls) who underwent colonoscopy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genotype and allele frequencies of the two polymorphisms. Regarding rs1544410 and CRA patients, genotype distribution was 35% B/B, 47% B/b, and 19% b/b. In the controls, the distribution was 21% B/B, 45% B/b, and 34% b/b. For rs2059806, 12% of CRA patients had A/A, 30% A/G, and 58% G/G, while 8% of the controls had A/A, 40% A/G, and 52% G/G. The recessive model showed an odds ratio of 2.84 (95% CI: 1.04-7.72, p = 0.033) for the b/b genotype. CRA patients with b/b or G/G genotypes were diagnosed at a younger age. The b allele of the rs1544410 was a risk factor for CRA. Patients with the b/b and G/G genotypes were diagnosed earlier.

The COVID-19 pandemic has raised awareness of the virus's long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C , and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T , dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID ( p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (β = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) ( p = 0.028 95% CI: 0.040-7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) ( p = 0.025 95% CI: 0.624-7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A , a difference in ventricular filling pressure (E/E'ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients.

Background: MASLD is a prevalent chronic liver condition with substantial clinical implications. This study aimed to assess the effectiveness of three new, elastography-based, scoring systems for advanced fibrosis ≥F3 (Agile 3+), cirrhosis F4 (Agile 4), and fibrotic NASH: NASH + NAS ≥4 + F≥2 (FAST score), in a cohort of biopsy-proven NAFLD meeting MASLD criteria. Our secondary aim was to compare their diagnostic performances with those of other fibrosis prediction tools: LSM-VCTE alone, and common, easily available scores (FIB-4 or APRI)., Methods: Single-center, retrospective study, on consecutive patients with baseline laboratory tests, liver biopsy, and reliable LSM-VCTE measurements. The discrimination between tests was evaluated by analyzing the AUROCs. Dual cut-off approaches were applied to rule-out and rule-in ≥F3, F4 and fibrotic NASH. We tested previously reported cut-off values and provided our best thresholds to achieve Se ≥85%, Se ≥90%, and Sp ≥90%, Sp ≥95%., Results: Among 246 patients, 113 (45.9%) were women, and 75 (30.5%) presented diabetes. Agile 3+ and Agile 4 demonstrated excellent performance in identifying ≥F3 and F4, achieving AUROCs of 0.909 and 0.968, while the FAST score yielded acceptable results in distinguishing fibrotic NASH. When compared to FIB-4 and LSM-VCTE, both Agile 3+ and Agile 4 performed better than FIB-4 and had a similar performance to LSM-VCTE, but with higher diagnostic accuracy, hence reducing the grey zone., Conclusion: Agile 3+ and Agile 4 are reliable, non-invasive tests for identifying advanced fibrosis or cirrhosis in MASLD patients, while FAST score demonstrates moderate performance in identifying fibrotic NASH., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Taru et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile ( p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients ( p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance ( p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

The role of the NLRP3 inflammasome is pivotal in the pathophysiology and progression of diabetes mellitus (DM), encompassing both type 1 (T1D), or type 2 (T2D). As part of the innate immune system, NLRP3 is also responsible for the chronic inflammation triggered by hyperglycemia. In both conditions, NLRP3 facilitates the release of interleukin-1β and interleukin-18. For T1D, NLRP3 perpetuates the autoimmune cascade, leading to the destruction of pancreatic islet cells. In T2D, its activation is associated with the presence of insulin resistance. NLRP3 activation is also instrumental for the presence of numerous complications associated with DM, microvascular and macrovascular. A considerable number of anti-diabetic drugs have demonstrated the ability to inhibit the NLRP3 inflammasome.

Background: interleukin 23 (IL-23) is an important factor involved in the survival and proliferation of T helper 17 cells (Th17), known for their implication in multiple sclerosis (MS). By contrast, IL-27 regulates and modulates the function of T lymphocytes, in particular as a suppressor of Th17 differentiation. The aims of the study were i) to test the association of cytokines with the clinical and genetic characteristics in each of the multiple sclerosis groups (CIS - clinically isolated syndrome, RRMS - relapsing-remitting MS and SPMS - Secondary progressive MS) and ii) to evaluate the association between serum levels of IL-23 and IL-27 with T4730C (IL-27), A964G (IL-27) and R381Q (IL-23) gene polymorphisms in RRMS patients., Methods: Blood samples were obtained from 82 patients diagnosed with MS under treatment with glatiramer acetate (GA), interferon beta (IFN) 1 A and 1 B. IL-23 and IL-27 serum concentrations were measured by enzyme-linked immunosorbant assay (ELISA). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used in order to determine the genotypes for R381Q (IL-23) polymorphisms, T4730C (IL-27) and A964G (IL-27)., Results: Patients with SPMS, RRMS and CIS respectively differed significantly regarding age distribution (p = 0.003) but the studied MS groups were similar regarding age at disease onset (p = 0.528) and treatment type (p = 0.479). A significant increase of mean serum IL-27 was noticed in cases with early onset (age at disease onset <28 years) of RRMS (mean difference: 4.2 pg/ml, 95% CI: 0.8-5.3 pg/ml), compared to cases with later onset of RRMS (age at disease onset ≥28 years). RRMS patients with wild GG genotype of R381Q (IL-23) showed a significant increase of mean serum IL-23 than patients with variant AG genotype (mean difference: 115.1 pg/ml, 95% CI: 8.6-221.6 pg/ml). A trend for a higher increase in means of serum IL-23 (p = 0.086) was observed in RRMS patients carriers of AA genotype of A964G (IL-27) polymorphism in comparison with patients with AG or GG genotypes. We found no significant monotonic correlation of IL-27, IL-23 serum levels with age at disease onset (years) and duration of disease (p > 0.05) in the CIS and SPMS group respectively but a significant correlation between IL-23 and the duration of disease-modifying treatment was noticed only in the SPMS group., Conclusions: The results of the current study suggest an association between IL-23 levels and the R381Q gene polymorphism and also a relationship between IL-27 serum levels and early age at disease onset in RRMS patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

(1) Background: Vascular endothelial growth factor (VEGF) is essential in vasculo- and angiogenesis due to its role in endothelial cell proliferation and migration. As a vascular proliferative factor, VEGF is one of the hallmarks of cancer and, in adult populations, the relationship between genetic polymorphism and neoplasm was widely investigated. For the neonatal population, only a few studies attempted to uncover the link between the genetic polymorphism of VEGF and neonatal pathology, especially related to late-onset complications. Our objective is to evaluate the literature surrounding VEGF genetic polymorphisms and the morbidity of the neonatal period. (2) Methods: A systematic search was initially conducted in December 2022. The PubMed platform was used to explore MEDLINE (1946 to 2022) and PubMed Central (2000 to 2022) by applying the search string ((VEGF polymorphism*) and newborn*). (3) Results: The PubMed search yielded 62 documents. A narrative synthesis of the findings was undertaken considering our predetermined subheadings (infants with low birth weight or preterm birth, heart pathologies, lung diseases, eye conditions, cerebral pathologies, and digestive pathologies). (4) Conclusion: The VEGF polymorphisms seem to be associated with neonatal pathology. The involvement of VEGF and VEGF polymorphism has been demonstrated for retinopathy of prematurity.

Non-alcoholic fatty liver disease (NAFLD), and its progressive form, non-alcoholic steatohepatitis (NASH), represent, nowadays, real challenges for the healthcare system. Liver fibrosis is the most important prognostic factor for NAFLD, and advanced fibrosis is associated with higher liver-related mortality rates. Therefore, the key issues in NAFLD are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. We critically reviewed the ultrasound (US) elastography techniques for the quantitative characterization of fibrosis, steatosis, and inflammation in NAFLD and NASH, with a specific focus on how to differentiate advanced fibrosis in adult patients. Vibration-controlled transient elastography (VCTE) is still the most utilized and validated elastography method for liver fibrosis assessment. The recently developed point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) techniques that use multiparametric approaches could bring essential improvements to diagnosis and risk stratification.

Polymorphism of insulin-like growth factor 2 (IGF2) is known to play a role in cell development. Only the paternal IGF2 copy is active, while the copy inherited from the mother is inactive. This study aimed to explore whether maternal and paternal factors influence IGF2 polymorphism in newborns with intrauterine growth restriction (IUGR) compared to appropriate for gestational age (AGA). A cross-sectional exploratory study was conducted from June 2014 to November 2015 at the Neonatology, Gynecology 1 Clinic, Cluj-Napoca, Romania. The ApaI IGF2 genotypes and allele frequencies were similar in the IUGR and AGA groups (p-value > 0.10). The IUGR babies with a protective IGF2 genetic profile had significantly younger parents (a difference in the median age of 8 years for mothers and 9 years for fathers; p-value < 0.009). The IUGR babies had parents with lower birth weights than AGA babies (mothers’ medians: 2800 g vs. 3100 g; fathers’ medians: 3000 g vs. 3400 g; p-value < 0.02). In univariable regression analysis, the mother’s and father’s birth weight proved to be associated with IUGR. The father’s birth weight proved to be the only factor significantly associated with IUGR, independent of the mother’s birth weight or the presence of a protective IGF2 genetic profile (odd ratio = 0.998 [0.996 to 1.000], p-value = 0.032).

(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730C (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27- T4730C gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14-7.83, p -value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05-3.51, p -value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p -value = 0.015, OR = 1.58, 95% CI: 1.09-2.28), while IL-23- R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08-0.92, p -value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p -value = 0.008, OR = 0.23, 95% CI: 0.07-0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C ( A964G , T4730C ) haplotype had a 3.18 increased risk (95% CI: 1.74-5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27- A964G and IL-27- T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23- R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C ( A924G , T4730C ) as a significant risk haplotype for the development of MS.

Hypertensive cardiac remodeling is illustrated by increased left ventricular (LV) mass index values and/or relative wall thickness (RWT) values >0.42, and functionally by isolated alteration of LV diastole (abnormal relaxation). The aim of the present study was to establish differentiated models of anatomical and functional adaptation to essential hypertension (EHT), in relation to the genetic variants of genes involved in the Renin-Angiotensin-Aldosterone System (RAAS). The M235T -AGT, I/D -ACE, A1166C -R1AngII, A3123C -R2AngII and G83A -REN genotypes were determined using PCR-Restriction Fragment Length Polymorphism in 139 hypertensive subjects. The relationship between the studied RAAS gene polymorphisms with morphological and functional cardiac remodeling was assessed by multiple logistic regression analysis. Patients carrying the C/C , A/C genotypes ( A3123C -R2AngII polymorphism) had a 2.72-fold (P=0.033) increased risk of exhibiting an RWT value <0.42; in the multivariate model the risk was 4.02-fold higher (P=0.008). Analysis of LV diastolic dysfunction (LVDD) revealed that hypertensive patients carrying the T/T , M/T genotypes ( M235T -AGT polymorphism) had a 2.24-fold (P=0.037) increased risk of developing LVDD and a 2.42-fold increased risk (P=0.039) after adjustment for confounders. Similarly, carriers of the G/G , A/G genotypes ( G83A -REN) had a 2.32-fold (P=0.021) increased risk of developing LVDD, and this remained an independent risk factor based on the multivariate model (P=0.033). The results of the present study showed that no particular gene was associated with increased LV mass, but the A3123C -R2AngII polymorphism was associated with a non-concentric type of cardiac response in hypertensive patients. Conversely, the M235T -AGT and G83A -REN polymorphisms were found to be statistically significantly associated with LVDD when assessing abnormal relaxation., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Mocan et al.)

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Multiple sclerosis (MS) is one of the most debilitating neurological diseases of young adults. The presence of a single nucleotide polymorphism in the promoter regions of the interleukin 27 gene (IL27 T4730C, rs181206) may alter the transcription and the production of cytokine levels, leading to MS., Patients and Methods: We performed a case-control study including 82 individuals: 51 patients diagnosed with MS and 31 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism was used in order to determine the genotypes for the IL27 T4730С polymorphism and enzyme-linked immunosorbent assay to measure the serum IL27 level., Results: Carriers of the T4730С polymorphism were found to have a 6-fold [95% confidence intervaI (CI)=1.83-19.63, p=0.002] increased risk for MS. Univariate logistic regression analysis showed an increased frequency of the TC4730 heterozygous genotype (39.2% vs. 9.7%) and also of the C4730 allele (27.45% vs. 8.06) in patients compared to controls, with a 6.02-fold increased risk (95% CI=1.61-22.46, p=0.006) and a 4.31-fold increased risk (95% CI=1.57-11.87, p=0.002) of developing MS. IL27 levels were significantly lower in patients compared to controls (12.35 versus 14.34 pg/ml, p=0.039), without significant differences between genotypes. Multivariate logistic analysis showed that IL27 T4730C polymorphism (odds ratio=6.272, 95% CI=1.84-21.40, p=0.003) and smoking (odds ratio=4.214, 95% CI=1.39-12.74, p=0.011) represented independent risk factors for MS., Conclusion: Our study provides a possible link between IL27 level and IL27 T4730C gene polymorphism and the risk for developing MS in a Romanian population., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

More than half of the patients with heart failure have preserved ejection fraction (HFpEF), however evidence shows a mortality rate comparable to those with reduced ejection fraction. The aim of this study was to evaluate whether FGF21, galectin-3 and copeptin can be used as biomarkers to identify HFpEF in patients with confirmed type 2 diabetes mellitus (DM). Sixty-nine diabetic patients were enrolled and divided into two groups: patients with HFpEF ( n = 40) and those without HFpEF ( n = 29). The ability of the studied biomarkers to discriminate HFpEF cases from non-HFpEF subjects were evaluated by the area under the Receiver Operating Characteristics (ROC) curve and the 95% confidence interval (CI). Compared to patients without heart failure, those with HFpEF had significantly higher levels of FGF21 (mean 146.79 pg/mL vs. 298.98 pg/mL). The AUC value of FGF21 was 0.88, 95% CI: [0.80, 0.96], Se = 85% [70.2, 94.3], Sp = 79.3% [60.3, 92.0], at an optimal cut-off value of 217.40 pg/mL. There was no statistical significance associated with galectin-3 and copeptin between patient cohorts. In conclusion, galectin-3 and copeptin levels were not effective for detecting HFpEF, while FGF21 is a promising biomarker for diagnosing HFpEF in DM patients.

Background/aim: The renin-angiotensin-aldosterone system (RAAS) may be implicated in carotid atheromatosis (CA) development. We aimed to assess the relationship of M235T-angiotensinogen (AGT) and insertion/deletion of angiotensin conversion enzyme (I/D-ACE) genotypes with CA in patients with essential hypertension (EHT)., Patients and Methods: We determined the M235T-AGT and I/D-ACE genotypes, using PCR-RFLP methods, in 162 hypertensive subjects from three tertiary regional medical centers. The relationship between the studied RAAS gene polymorphisms and CA was assessed by multiple logistic regressions., Results: Hypertensive patients carrying the MT/TT235-AGT and MT235-AGT genotypes had a 2.17-fold (p=0.033) and 2.24-fold (p=0.036) increased risk to develop CA, respectively. These genotypes, MT/TT 235-AGT (OR=2.17, p=0.033) and MT235-AGT (OR=2.24, p=0.036), remain independent risk factors for CA in hypertensive patients according to the multivariate model., Conclusion: There is a statistically significant association between M235T-AGT and CA, when adjusting for several confounders and controlling for hypertension., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Epidemiological studies have strongly associated lower levels of vitamin D and its metabolites with an increased risk of colorectal cancer (CRC). The action of calcitriol, the active metabolite of vitamin D, is mediated by the vitamin D receptor (VDR) that is present in most tissues. In advanced CRC, VDR expression is lowered. Calcitriol has several antineoplastic effects in CRC: it promotes the G1-phase cycle arrest, lowers vascular endothelial growth factor (VEGF) synthesis and acts on tumour stromal fibroblasts to limit cell migration and angiogenesis. Hyperinsulinemia and insulin-like growth factors (IGFs) have been implicated in the pathophysiology of CRC. IGF-1 and IGFBP-3 have been the most studied components of the IGF system. Only 1% of the total serum IGF-1 is free and bioactive, and 80% of it binds to IGFBP-3. IGF-1 and its receptor IGF-1R are known to induce cell proliferation. Both IGF-1 and IGFBP-3 can favour angiogenesis by increasing the transcription of the VEGF gene. A high serum IGF-1/IGFBP-3 ratio is associated with increased risk for CRC. VDR is a transcription factor for the IGFBP-3 gene, and IGF-1 can increase calcitriol synthesis. Studies examining the effect of vitamin D treatment on serum IGF-1 and IGFBP-3 have not been in agreement since different populations, dosages and intervention periods have been used. New vitamin D treatment studies that examine CRC should take in account confounding factors such as obesity or VDR genotypes., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Changes in the renin-angiotensin-aldosterone system's (RAAS) activity due to different genetic variations could represent risk factors for the onset of preeclampsia., Objective: To test and quantify the relationships of 8 RAAS gene polymorphisms (angiotensinogen (AGT)-M235T, AGT-T174M, angiotensin converting enzyme (ACE)-I/D, ACE8-A2350G, angiotensin II type 1 receptor (AGTR1)-A1166C, angiotensin II type 2 receptor (AGTR2)-C3123A, renin (REN)-G83A, aldosterone synthase (CYP11B2)-T344C) with susceptibility to early- (EOPE) and late-onset preeclampsia (LOPE)., Study Design: We performed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis in 217 pregnant women, of whom 87 pregnant women with EOPE/LOPE and 130 normal pregnant women. The relationship between the studied RASS gene polymorphisms and EOPE/LOPE was tested by multiple logistic regressions., Results: The multivariate logistic regression analysis showed that AGT-M235T (adjusted OR = 4.63), AGT-T174M (adjusted OR = 4.13), REN-G83A (adjusted OR = 3) and CYP11B2-C344T (adjusted OR = 3.13) gene polymorphisms remained independent risk factors for EOPE. Moreover, ACE-I/D (adjusted OR = 4.04), ACE-A2350G (adjusted OR = 3.5), AGTR1-A1166C (adjusted OR = 2.73), and REN-G83A (adjusted OR = 2.67) polymorphisms remained independent risk factors for LOPE. The frequency of overweight was significantly different (p = 0.001) in pregnant women with EOPE, LOPE and the control group (LOPE:16, 29.6% vs. EOPE:12, 36.4% vs. control group:16, 12.3%). Pregnant women with EOPE had babies with a significantly lower mean birth weight (2067.9 ± 887.9) in comparison to women with LOPE (mean ± SD: 2860.1 ± 771.1, p < 0.001) and women with normal pregnancies, respectively (mean ± SD: 3324.9 ± 484.9, p < 0.001)., Conclusion: We confirmed the influence of the renin-angiotensin-aldosterone system through these 8 genetic variations on the onset of preeclampsia., (Copyright © 2019. Published by Elsevier B.V.)

Background: Neonatal sepsis represents one of the common diseases in the neonatal intensive care unit. Here we aim to evaluate the differences between a group of preterm newborns with sepsis and a control group in relation to clinical and laboratory variables. In addition, our goal is to establish potential predictors of early-onset sepsis (EOS) and late-onset sepsis (LOS)., Methods: The study included 113 preterm newborns with sepsis (EOS-63.72%/LOS-36.28%). Laboratory deter-minations included full blood count, CRP, biochemical determinations, blood culture., Results: The most important univariate neonatal predictors were gestational age (p < 0.001), surfactant adminis-tration (p < 0.001), mechanical ventilation (p < 0.001), heart failure (p < 0.001), a history of hypocalcemia (p = 0.037), Apgar score at 1 minute lower than 7 (p = 0.001), birth weight < 1,500 g (p = 0.005), number of hospi-talization days (p = 0.048), and number of weight recovery days < 10 (p < 0.05). The WBC and CRP parameters remained significant univariate predictors of sepsis on day 7 (p = 0.002; OR = 2.01 per 10,000 mm3 increase of WBC, 95% CI: (1.30; 3.09) and p = 0.001; OR = 4.27, 95% CI: (1.85; 9.88), respectively). Logistic regression anal-ysis showed maternal urinary tract infection (OR = 3.05), heart failure (OR = 5.28), the number of hospitalization days (OR = 1.09) and CRP (OR = 3.26) were significant independent risk factors for neonatal sepsis in preterms. The univariate predictors of EOS were gestational age (p = 0.002), birth weight (p = 0.014), 1-minute Apgar score (p = 0.012), maternal urinary tract infection (p = 0.008), surfactant administration (p < 0.001), heart failure (p < 0.001), and CRP level (p < 0.001). Surfactant administration (OR = 6.73) and CRP level (OR = 3.51) represent predictors of EOS in preterms according to the multivariate model. The univariate predictors of LOS were gesta-tional age (p = 0.001), birth weight (p = 0.048), 1-minute Apgar score (p = 0.001), surfactant administration (p < 0.001), hypocalcemia (p = 0.03), heart failure (p = 0.003), CRP level (p < 0.001), mechanical ventilation (p < 0.001), and the number of hospitalization days (p < 0.001). In the multivariate model, the number of hospitali-zation days (OR = 1.11) and heart failure (OR = 5.98) are independent predictors for LOS in preterms., Conclusions: The study confirms the presence of maternal urinary tract infection, hospitalization days, heart fail-ure, and CRP level as predictors of neonatal sepsis in preterms with differences between EOS and LOS.

Purpose: The aim of our study was to evaluate the IGF2 and IGF2R plasmatic level and IGF2-ApaI polymorphism on infants with intrauterine growth restriction (IUGR)., Materials and Methods: A transversal study was conducted at the Neonatology Ward of the Gynecology Clinic I, Emergency Hospital Cluj-Napoca on neonates with IUGR who were discharged during June 2014 and June 2015. The serum levels of IGF2 and IGF2R were obtained by using ELISA method and IGF2-ApaI polymorphism by taking PCR-RFLP analysis., Results: Forty infants with IUGR and 21 infants of appropriate gestational age (AGA) were evaluated. The serum levels of IGF2 proved higher on the A/G genotype when the IUGR group was compared with AGA (p value = .048). The G allele proved significantly more frequent in both the IUGR and the AGA group compared with the A allele (p < .002). Neither any allele nor any genotype proved a risk factor for IUGR (p value > .3). The A/G genotype proved significantly more frequent on term infants compared with preterm infants (p value = .039)., Conclusions: The infant with IUGR has a higher serum level of IGF2 if has A/G IGF2-ApaI genotype and higher values of IGF2R if it has the A/A genotype.

Objectives: The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes., Methods: Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis., Results: The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A, and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (P<.001), 7.7 (P<.001), 7.83 (P<.001), 7.51 (P<.001), and 8.62 (P<.001), respectively. Alcohol consumption associated with the NAT2 -T341C, G590A, G857A, A845C, and C481T rapid acetylator allele induces a risk of 10.63 (P<.001), 12.04 (P<.001), 9.76 (P<.001), 10.25 (P<.001), and 9.54 (P<.001), respectively, for colon cancer, whereas the risk for rectal cancer is 9.72 (P<.001), 11.24 (P<.001), 13.07 (P<.001), 10.04 (P<.001), and 9.43 (P<.001), respectively. Smokers with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele have a risk of 4.87, 4.25, 4.18, 3.81, and 3.82, respectively, to develop colon cancer., Conclusions: Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants., (© 2016 Wiley Periodicals, Inc.)

Background: The molecular mechanism of carcinogenesis of sporadic colorectal cancer (CRC) involves genes with roles in folate metabolism, genes involved in metabolization of carcinogenic compounds from diet and tobacco smoke, and genes related to the DNA repair process. The aim of the study was to examine whether the MTHFRC677T, MTHFR- A1298C, TS-2rpt/3rpt, TS-1494del6bp, NAT2*5C-C481T, NAT2*5A-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, GSTM1-null, XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln genetic variations are associated with CRC prognosis, in the presence of environmental and demographic factors., Methods: We genotyped 150 patients diagnosed with sporadic CRC using PCR-RFLP and sequencing methods. The performance of the final model was quantified using Nagelkerke's coefficient, the Hosmer-Lemeshow test, C statistics, and Somers' (D) index, capable of describing the model's goodness-of-fit and discrimination., Results: Multiple logistic regression analysis established a significant independent association of NAT2*18-A845C, MTHFR-C677T, XRCC3-Thr241Met, NAT2*7B-G857A, XPD-Lys751Gln, XRCC1-Arg399Gln and NAT2*6BG590A with an increased prevalence of sporadic CRC, regardless of the presence/absence of colonic tumors. After an adjustment for other polymorphisms and environmental risk factors, the risk to develop sporadic CRC was 2.25 (p = 0.011) and 2.31 (p = 0.01) in association with the NAT2*18-A845C and MTHFR-C677T genetic variants, respectively. The risk increased to 3.22 (p = 0.0005) and 3.69 (p = 0.0009) in association with the XRCC3Thr241Met and NAT2*7B-G857A polymorphisms. Also, patients carrying the XPD-Lys751Gln, XRCC1Arg399Gln, and NAT2*6B-G590A polymorphisms had a 4.16 (p < 0.0001), 5.16 (p < 0.0001), and 5.46-fold (p < 0.0001) increased risk for sporadic CRC, under the dominant genetic comparison model. In addition, we found an interaction between gender and alcohol, the effect of alcohol consumption on the risk of developing sporadic CRC being different in female and male patients., Conclusions: Our study confirmed the predictive role of some polymorphisms associated with DNA methylation and procarcinogen transformation into carcinogenic compounds in sporadic CRC risk and, also, the influence of environmental risk factors such as diet, smoking, and alcohol consumption on this association.

Aim: To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia., Materials and Methods: We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA., Results: Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia., Conclusion: The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

Aim: To establish the role of the interaction between maternal and newborn apolipoprotein E (APOE) genotypes on the risk, lipid profile and prognosis of preeclampsia (PE)., Materials and Methods: Forty-seven preeclamptic women and 94 normotensive pregnant women and their newborns were genotyped for APOE using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis., Results: Maternal APOE-ε4 allele was associated with an about eight times higher risk of PE (adjusted OR = 8.4, 95% CI: 2.51-28.17, p = 0.001). The multivariate logistic regression model showed that the newborn APOE-ε4 allele was associated with an about six times higher risk of PE (adjusted OR = 5.6, 95% CI: 2.09-15.21, p = 0.001) for the given gestational age levels. Pregnant women with severe PE whose newborns carried the APOE-ε4 allele delivered at earlier gestational ages neonates with a lower birth weight compared to pregnant women with newborns negative for this allele. Higher TG and LDL-C levels and lower HDL-C levels were found in pregnant women with severe PE whose newborns were carriers of the APOE-ε4 allele compared to preeclamptic women whose newborns were carriers of the ε3/ε3 genotype. If we checked the combined effect of the mother/newborn genotypes on the risk of PE, we found that the risk to develop PE was 15.4-fold (p < 0.001) increased if mothers or newborns were carriers of the APOE-ε4 allele. The risk increased to 20.02 (p < 0.001) if both the mother and newborn were carriers of the APOE-ε4 allele., Conclusions: Our study confirms the maternal/newborn APOE genotype interaction influences the risk for PE, as well as prognosis and lipid profile.

Objective: To analyze the influence of maternal/newborn vascular endothelial growth factor (VEGF)-CT936 interaction as a modulating factor in preeclampsia as well as its influence on the maternal angiogenic balance., Methods: Seventy pairs of preeclamptic women/newborns and 94 pairs of normal pregnant mothers/newborns were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum VEGF and soluble VEGF receptor-1 (sVEGFR-1) levels were measured using ELISA., Results: The risk to develop mild (odds ratio; OR: 3.79, p = 0.008) and severe (OR: 2.94, p = 0.037) preeclampsia being increased in association with the CT936-VEGF genotype and increased in severe preeclampsia to 6.07 (p = 0.03) if the women were carriers of the homozygous TT936-VEGF genotype. The presence of the VEGF-T936 allele in both the mother and the newborn significantly increases the risk of pregnancy-induced hypertension (PIH), mild and severe preeclampsia. If both the mothers and newborns were carriers of the VEGF-T936 allele, significantly lower VEGF and higher sVEGFR-1 levels were observed for all types of preeclampsia. Pregnant women with PIH and severe preeclampsia delivered at a significantly earlier gestational age neonates with a significantly lower birth weight if both the preeclamptic mothers and their newborns were carriers of the VEGF-T936 allele., Conclusions: Our study suggests the role of maternal/fetal VEGF-CT936 polymorphism as a modulating factor in preeclampsia, which affects the angiogenic balance in preeclamptic mothers, as well as their pregnancy outcome.

Aim: To establish that newborn Ser447Stop and Asn291Ser may have interactive effects with maternal genotypes on the plasma lipoprotein levels, risk of preeclampsia as well as on the prognosis of preeclampsia., Materials and Methods: Seventy preeclamptic women and 94 normotensive pregnant women, and their newborns were genotyped using PCR-RFLP methods., Results: The risk of mild and severe preeclampsia was 4 (p = 0.004) and 5.18 (p = 0.001), respectively, if both the mother and newborn were carriers of the Ser447/Ser477 genotype. If both the mother and newborn were carriers of the Asn291Ser variant, the risk to develop severe preeclampsia was 6.07 (p = 0.03). Women with mild and severe preeclampsia had higher TG (p < 0.001; p < 0.001) and LDL-C levels (p = 0.008; p < 0.001) if both the mother and newborn were carriers of the Ser447/Ser447 genotype. Women with severe preeclampsia had significantly higher TG (p = 0.03) and LDL-C levels (p = 0.037) if both the mother and newborn were carriers of Asn291Ser. Newborn/maternal LpL interaction had no statistically significant influence on pregnancy outcome., Conclusions: The newborn/maternal LpL interaction influences the severity of preeclampsia and modulates the lipid profile particularly in severe preeclampsia.

We evaluated the association between the presence of the GSTM1-null genotype and the combined presence of the GSTM1-null genotype/NAT2 rapid acetylator phenotype and the risk of developing sporadic colorectal cancer (CRC), as well as their interaction with environmental risk factors. One hundred and fifty patients with sporadic CRC and 162 controls were genotyped using PCR-RFLP analysis. For testing and quantification of the simple effect (main effect) and of the gene-gene and gene-environment interaction (modification effect), univariate and multivariate logistic regression was used. In the multiplicative model, from the genetic factors, GSTM1-null and NAT2*6B had a statistically significant influence on the risk for CRC, while from the environmental factors, smoking and diet had similar effects. The combination of GSTM1-null/NAT2 rapid acetylator phenotype/smoking behavior or GSTM1-null/NAT2 rapid acetylator phenotype/diet rich in fried red meat was not found to influence the sporadic CRC risk in Romanians, but the GSTM1-null genotype, NAT2 rapid acetylator phenotype influenced the sporadic CRC risk differently depending on the gender of the patient.

Objectives: To investigate the role of LPL-Ser447Ter and Asn291Ser polymorphisms in the predisposition to different types of preeclampsia, as well as the contribution to the lipid profile and the prognosis of preeclampsia., Methods: 125 women with preeclampsia and 131 normal pregnant women were genetically screened using PCR-restriction enzyme analysis., Results: We found an increased risk for mild and severe preeclampsia in carriers of the negative Ser447/Ser447 genotype. An increased risk for severe preeclampsia in carriers of the Asn291Ser polymorphism was seen. In mild and severe preeclampsia, carriers of the negative Ser447/Ser447 genotype had increased TG and LDL-C levels and decreased HDL-C levels as compared with carriers of the Ser447Ter polymorphism. The presence of the Asn291Ser polymorphism influenced the higher TG and LDL-C levels and the lower HDL-C levels in mild preeclampsia and the higher TG and LDL-C levels in severe preeclampsia. Women with severe preeclampsia, carriers of the Ser447/Ser447 genotype and women with mild preeclampsia, carriers of the Asn291Ser polymorphism, delivered at a lower gestational age neonates with a lower birth weight compared to women carriers of this polymorphism., Conclusions: The LPL variants are associated with severe preeclampsia and influence the lipid profile and pregnancy outcome in mild and severe preeclampsia.

Background: DNA repair processes involved the removal of modified bases through the base excision repair (BER) pathway and removal of damaged nucleotides through the nucleotide excision repair (NER) pathways., Methods: in order to determine the association between XPD(Lys751Gln) and XRCC1 (Arg399Gln) SNPs and the risk of CRC as well as tumor grade and stages in Romanians we genotyped using PCR-RFLP methods 150 patients (80 females and 70 males) and 162 controls (100 females and 62 males)., Results: The risk (odds ratio - OR) to develop sporadic CRC was 3.02 (p=0.02) and 3.49 (p=0.001), respectively, in association with the homozygous Gln751 Gln751-XPD and Gln399 Gln399-XRCC1 genotypes. Higher risk for carriers of the Gln751 Gln751 - Arg399 Arg399 (OR 4.19, p=0.027),Gln399 Gln399 - Lys751 Lys751 (OR 3.21, p=0.013),Gln399 Gln399 - Lys751 Gln751 (OR 4.5, p=0.05),Lys751 Gln751 - Arg399 Gln399 (OR 3.94, p 0.001) combined genotypes was observed. The lowest risk was observed in carriers of Lys751 Lys751-Arg399 Arg399 genotypes (OR0.24, p 0.001). 2.24-fold (p=0.05) and 3.75-fold (p=0.004)increased risk (OR) for carriers of the Lys751Gln or Arg399Gln variants to be on stage pT2 and pT4, respectively. Patients carriers of Lys751Gln or Arg399Gln variants had 7.7-fold(p=0.002) and 18.94-fold (p 0.001) increased risk (OR) to develop sporadic CRC in stage D., Conclusions: XPD and XRCC1 variants affect the risk for sporadic CRC in Romanians, seem to be associated with more aggressive forms of sporadic CRC and may be prognostic factors in patients with advanced CRC., (Celsius.)

Objective: To check whether individual or combined mutated genotypes for Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) are associated with preeclampsia; to check the influence of the mutated genotypes on the degree of severity and perinatal outcome of preeclampsia., Methods: We genotyped 97 pregnant women (47 with preeclampsia and 50 normal pregnant women) using PCR-RFLP analysis., Results: The Val/Val (Mn-SOD) genotype (OR 5.99, p = 0.004) but not the Gly/Gly (EC-SOD) genotype (OR 4.23, p = 0.027) was significantly associated with preeclampsia. Higher frequency of both polymorphisms in women with preeclampsia (42.55%) compared to normal pregnant women (8%). Higher frequency of women diagnosed with PIH (27.27%, OR 4.31), mild (50%, OR 11.5) and severe preeclampsia (37.5%, OR 6.9) positive for both polymorphism compared to control women (8%). There was a statistically significant difference in gestational age at delivery according to Mn-SOD (Ala/Ala vs. Val/Val, 39 ± 1.41 weeks vs. 32.77 ± 3.7 weeks) and EC-SOD genotypes (Arg/Arg vs. Gly/Gly, 37.05 ± 3.18 weeks vs. 31.5 ± 3.84 weeks). There also was a statistically significant difference in birth weight according to Mn-SOD (grams, Ala/Ala vs. Val/Val, 3080 ± 481.66 vs. 2376.92 ± 916.88) and EC-SOD genotypes (grams, Arg/Arg vs. Gly/Gly, 2934.09 ± 662.14 vs. 2080 ± 721.19)., Conclusions: Our study demonstrates a relationship between these two mutated genes, the clinical severity and the perinatal outcome of preeclampsia.

Aim: To investigate the biochemical and genetic thyroid status in women with preeclampsia by the determination of serum FT3 and FT4 levels in association with D1-C785T genotypes., Methods: We genotyped using PCR-RFLP methods 50 women with preeclampsia and 50 normotensive pregnant women., Results: FT3 levels (pg/ml, 2.63 ± 0.56 vs. 2.91 ± 1.41) were low, and FT4 levels (ng/dl, 1.11 ± 0.3 vs. 0.88 ± 0.14) were high in women with preeclampsia compared to normal pregnant women. The association with severe preeclampsia was stronger for the homozygous T/T genotype (OR 6.57, p = 0.029). Women with preeclampsia with the D1-T785 mutated allele had lower FT3 levels (pg/ml, 2.31 ± 0.81 vs. 3.04 ± 0.39, p < 0.001), higher FT4 levels (ng/dl, 1.32 ± 0.87 vs. 0.84 ± 0.24, p = 0.009) than women with preeclampsia with the D1-C/C genotype. Significant decrease in serum FT3 levels in positive women with severe preeclampsia compared to women negative for this genetic variation (pg/ml, 1.59 ± 0.74 vs. 2.77 ± 0.23, p = 0.003) was observed. Women with severe preeclampsia, positive for the mutated T785 allele, delivered at a significantly lower gestational age (31.75 ± 3.69 vs. 38.66 ± 3.21 weeks, p = 0.035) neonates with a lower birth weight (1861.11 ± 869.9 vs. 3500 ± 424.26 g, p = 0.023) compared to women negative for the same allele., Conclusions: Thyroid hormone levels and the D1-C785T polymorphism, alone or in combination, correlate with the severity of preeclampsia. The D1-C785T polymorphism influences the outcome of pregnancy in severe preeclampsia.

Introduction: We evaluated the association of the mutated genotypes Met235Thr-AGT, Thr174Met-AGT, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A-AT2R2, (83)A/G-REN with the risk and outcome of pre-eclampsia; we also investigated whether genes in newborns increase maternal risk of pre-eclampsia., Materials and Methods: Thirty-six pairs of pre-eclamptic women and their newborns were genotyped, along with 71 pairs of controls (mothers/newborns) using PCR-RFLP analysis., Results: The Thr235/Thr235 (OR 3.44, p = 0.01), DD (OR 2.66, p = 0.039), CC1166 (OR 5.56, p = 0.04), AA3123 (OR 3.77, p = 0.03) and GG(83) (OR 8.32, p = 0.006) genotypes are significantly associated with pre-eclampsia. Women with pre-eclampsia positive for Met235Thr (34.64 ± 3.92 weeks vs. 38 ± 2 weeks), Thr174Met (32.58 ± 3.92 weeks vs. 36.38 ± 3.25 weeks), I/D (34.47 ± 3.67 weeks vs. 38.33 ± 3.5 weeks) delivered at a significant lower gestational age compared with pre-eclamptic women with a normal genotype. Newborns from women with pre-eclampsia positive for Thr174Met (2190 ± 820.21 g vs. 2702.08 ± 967.23 g), I/D (2399.33 ± 938.38 g vs. 3191.66 ± 684.40 g) had a significant lower birth weight compared with newborns from women with normal pregnancies. When both the mother and the newborn were positive for Met235Thr, I/D, A2350G, A1166C or (83)A/G polymorphisms, the risk for pre-eclampsia was significantly increased at 6.67 (p < 0.01), 5 (p < 0.01), 3.33 (p = 0.006), 2.72 (p = 0.04) and 7.8 (p < 0.01), respectively., Conclusions: The results of our study confirm that, in pre-eclampsia, both maternal and newborn genetic variations implicated in blood pressure regulation are important.

Aim: To analyze the influence of thyroid stimulating hormone (TSH) levels and/or the Asp727Glu polymorphism on the severity and perinatal outcome of preeclampsia., Methods: Forty-nine women with preeclampsia and 58 normal pregnant women were genotyped for the TSHRc-Asp727Glu polymorphism using PCR-RFLP methods. The plasma TSH levels were measured by ELISA method., Results: Fourteen (77.78%) women of 18 pregnant women with abnormal TSH levels had preeclampsia compared to 35 (39.33%) of 89 pregnant women with normal TSH levels who had preeclampsia (OR 5.4, p = 0.003). The mean TSH levels were 2.13 ± 1.44 μU/ml, 2.47 ± 2.03 μU/ml and 4.27 ± 2.75 μU/ml in women with pregnancy induced hypertension (PIH), mild and severe preeclampsia, respectively. OR for PIH and mild preeclampsia was 1.08 (p = 1) and 9.45 (p = 0.06), respectively, in association with the Asp/Asp genotype. All women with severe preeclampsia had the Asp/Asp genotype. The risk for preeclampsia in association with TSH > 4 μU/ml and Asp/Asp genotype is 20.8 (p < 0.01). Preeclamptic women with TSH levels > 4 μU/ml and the Asp/Asp genotype delivered earlier (weeks, 34.92 ± 4.33 vs. 36.6 ± 3.21, p = 0.3) neonates with lower birth weight (grams, 2361.54 ± 1155.81 vs. 3000 ± 1072.38, p = 0.3) than preeclamptic women with TSH levels  < 4 μU/ml and the Asp/Glu genotype., Conclusions: Higher TSH levels and/or the TSHRc-Asp727Glu polymorphism represent risk factors for preeclampsia and could be correlated with the severity of preeclampsia.

Background: The genes associated with hypertension could be genetic risk factors for metabolic syndrome (MetS)., Aim: To determine the frequency of M235T and T174M-AGT, I/D-ACE and A1166C-AGTR1 in hypertensive patients with MetS and to evaluate the relationship between these polymorphisms and central obesity and dyslipidemia, respectively., Materials and Methods: We performed AGT, AGTR1 and ACE genotyping in 56 hypertensive women (24 with MetS) and 71 normotensive women using PCR-RFLP methods and PCR, respectively., Results: Hypertensive patients carrying the mutated TT235, MM174 and DD genotypes had an 1.53 (p=0.56), 1.78 (p=0.52) and 1.28 (p=0.78)-fold increased risk to develop MetS. Hypertensive carriers of both mutated TT235 and MM174 or TT235 and D/D or TT235 and CC+AC genotypes had an 8.15 (p=0.04), 4.83 (p=0.04) and 10.53 (p=0.05)-fold increased risk to develop MetS. Hypertensive patients with MetS and TT, D/D or CC genotypes had higher body mass index compared to hypertensive patients without MetS (p

Several lines of evidence have implicated the gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) in susceptibility to various autoimmune diseases. However, published studies of genetic association between CTLA4 polymorphisms and vitiligo have yielded conflicting results. Here, we describe two new genetic association studies of CTLA4 single-nucleotide polymorphisms (SNPs) and generalized vitiligo in two independent Romanian Caucasian (CEU) case-control cohorts. The first study, of SNPs rs1863800, rs231806, rs231775, rs3087243, rs11571302, rs11571297, and rs10932037, showed no allelic, genotypic, or haplotypic association with generalized vitiligo. The second study, of SNP rs231775, likewise showed no significant association. To enhance statistical power over that of any individual study, we carried out a meta-analysis that incorporated these two new studies and all other published genetic association studies of CTLA4 SNPs and vitiligo in CEU populations. While there was no association with vitiligo overall, the meta-analysis showed significant association of SNP rs231775 in that subgroup of vitiligo patients who also had other concomitant autoimmune diseases. Similarly, there was near-significant association in this same patient subgroup with several other CTLA4 SNPs that are in linkage disequilibrium with rs231775. Our results indicate that the association of CTLA4 with vitiligo is weak, and indeed may be secondary, driven by primary genetic association of CTLA4 with other autoimmune diseases that are epidemiologically associated with vitiligo.

Genetic mutations of the coagulation factors II and V (G20210A and G1691A - factor V Leiden)--as well as the one for methylene tetrahydrofolat reductase's (MTHFT) gene C677T are diseases with dominant autosomal transmission characterized by thromboembolic events leading to deep vein thrombosis and/or pulmonary embolism. The authors show the clinical observation of 2 cases of recurrent deep venous thrombosis evolving with pulmonary embolism in patients with genetic defects of the coagulating factors. The positive diagnostic was put on the paraclinical findings and the etiology was established from the homocysteine genetic modification of the G20210A prothrombin and factor V Leiden and MTHFT mutation. Publishing these cases will allow us to emphasize the importance of the genetic factors for thromboembolic episodes and especially for the consequences of the long-term anticoagulant therapy.

Background: Several studies suggested the role of the genes of the rennin-angiotensin system in the pathogenesis of essential arterial hypertension., Patients: We investigated 100 consecutive hypertensive patients (42 males and 58 females; mean +/- SD age, 55.14 +/- 9.49 years) for M235T and T174M polymorphisms. Seventy six normotensive patients (28 males and 48 females; mean +/- SD age, 54.94 +/- 9.56 years) formed the control group., Methods: M235T and T174M polymorphisms were analyzed using PCR-RFLP methods., Results: The carrier frequency of M235T polymorphism in the AGT gene was 73% in hypertensive patients and 34.21% in normotensive patients (OR 5.2, 95%CI [2.72-9.93], p<0.01, chi2 test). The carrier frequency of T174M polymorphism in the AGT gene was 42% in hypertensive patients and 11.84% in normotensive patients (OR 5.39, 95%CI [2.41-12.01], p<0.01, chi2 test)., Conclusions: Essential arterial hypertension is associated with polymorphisms in the AGT gene, M235T and T174M.

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.