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AbstractThe inflammatory cytokine resistin, which is encoded by the RETN gene, plays a variety of roles in cancer. This study aimed to assess the relationship between RETN gene expression and cancer stage, survival prognosis, immune infiltration, and drug sensitivity, and whether the rs3219175 G > A polymorphism affected the expression of the RETN gene and cancer risk. The clinical significance of RETN gene expression and the rs3219175 polymorphism in cancer was analyzed by the GSCA platform, GTEx database and STATA software. The results showed that RETN gene expression was associated with the stage of thyroid carcinoma, survival prognosis and immune infiltration of certain cancers, and sensitivity to multiple drugs. The rs3219175 polymorphism could influence the expression of the RETN gene in a wide range of tissues. Furthermore, RETN gene rs3219175 polymorphism was significantly associated with cancer risk [GA vs. GG: OR = 2.27, 95%CI = 1.26–4.09; (GA + AA) vs. GG: OR = 2.23, 95%CI = 1.28–3.88; A vs. G: OR = 1.72, 95%CI = 1.15–2.58]. In conclusion, the current study suggested that resistin might serve as a prognostic marker and therapeutic target for certain cancers, and the rs3219175 polymorphism might be used as a marker for predicting cancer risk. [ABSTRACT FROM AUTHOR]

Abstract Background Evidence suggests that circulating resistin levels are altered in colorectal cancer (CRC) and breast cancer (BC). Again, polymorphisms in resistin-encoding gene RETN have been evaluated in CRC and BC. However, there is a scarcity of data establishing the relationship of resistin and RETN polymorphisms (rs1862513 and rs3745367) with these cancers. This study aimed to analyze the relationship of resistin levels and RETN polymorphisms with CRC and BC in a combined meta-analytic approach. Main body of the abstract After a comprehensive online literature search, screening and eligibility check, 41 articles (31 with resistin level and 10 with RETN polymorphisms) were retrieved for meta-analyses. The mean difference (MD) of resistin was calculated and pooled to investigate the effect sizes with a 95% confidence interval (CI), and the connection of genetic polymorphisms was analyzed with an odds ratio (OR) and 95% CI. The analysis showed that resistin level is significantly higher in CRC (MD = 3.39) and BC (MD = 3.91) patients. Subgroup analysis in CRC showed significantly higher resistin in serum (MD = 4.61) and plasma (MD = 0.34), and in BC, a significantly elevated resistin level was reported in premenopausal (MD = 7.82) and postmenopausal (MD = 0.37) patients. Again, RETN rs1862513 showed a significantly strong association with CRC (codominant 1—OR 1.24, codominant 2—OR 1.31, dominant model—OR 1.25, and allele model—OR 1.16) and with BC (codominant 2—OR 1.51, codominant 3—OR 1.51, recessive model—OR 1.51, and allele model—OR 1.21). RETN rs3745367 did not show any association with these cancers. Short conclusion Overall, our analysis indicates that higher circulating resistin levels are associated with an elevated risk of CRC and premenopausal and postmenopausal BC. Besides, rs1862513 in RETN gene is significantly connected with both CRC and BC.

Background: The published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research. Methods: PubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0. Results: A total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87-1.10, pheterogeneity <.001; I² = 84.6%; for the dominant model: OR = 0.96, 95% CI = 0.80-1.15, pheterogeneity <.001; I²=87.1%; andfor the recessivemodel: OR=0.96,95%CI = 0.82-1.12, pheterogeneity <.001; I² = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; pheterogeneity <.001; I² = 80.9%)] and decreased risk in older people [for dominant: OR = 3.14 (95% CI, 2.35-4.19; pheterogeneity = .98; I² = 0.0%)]. Conclusions: Current results found no evidence that the RETN -420C/G variant was linked to T2DM susceptibility, but the patient's age appears to be a potential factor that contributed to high heterogeneity across studies. Additional high-quality and well-designed investigations are required to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris is a highly prevalent skin disorder that involves pilosebaceous units and may have adverse psychological effects on patients. The occurrence of acne is multifactorial and closely related to the interplay of environmental and genetic factors. Aim: To investigate the possible association between RETN‐420C>G, IL6‐572G>C, and IL1A‐889C>T polymorphism and acne vulgaris in the Chinese population. Methods: In this case‐control study, genotyping was conducted in 306 patients with acne and 306 healthy controls by using polymerase chain reaction and snapshot technique. Results: There is a strong correlation between RETN‐420 and IL6‐572 polymorphisms and acne susceptibility; the RETN‐420G and IL6‐572C alleles increase the risk of acne development. We also found that IL6‐572G>C gene polymorphism is significantly associated with family history of acne and acne severity. In contrast to previous studies, we found no significant difference in the IL1A‐889C>T polymorphism between healthy controls and acne patients in our population. Conclusion: Our findings provide the first evidence that RETN‐420 and IL6‐572 gene polymorphisms contribute to the pathogenesis of acne in the Chinese population. [ABSTRACT FROM AUTHOR]

Abstract Background Gestational diabetes mellitus (GDM) has significant short and long-term health consequences for both the mother and child. There is limited but suggestive evidence that inulin could improve glucose tolerance during pregnancy. This study assessed the effect of inulin on glucose homeostasis and elucidated the molecular mechanisms underlying the inulin-induced antidiabetic effects during pregnancy. Method Female C57BL/6 mice were randomized to receive either no treatment, high-dose inulin and low-dose inulin for 7 weeks with measurement of biochemical profiles. A real-time2 (RT2) profiler polymerase chain reaction (PCR) array involved in glycolipid metabolism was measured. Results Inulin treatment facilitated glucose homeostasis in a dose-dependent manner by decreasing fasting blood glucose, advanced glycation end products and total cholesterol, and improving glucose tolerance. Suppressing resistin (RETN) expression was observed in the inulin treatment group and the expression was significantly correlated with fasting blood glucose levels. The ratios of p-IRS to IRS and p-Akt to Akt in liver tissue and the ratio of p-Akt to Akt in adipose tissue as well as the expression level of GLUT4 increased significantly after inulin treatment. Conclusions Our findings indicated improvement of glucose and lipid metabolism by inulin was to activate glucose transport through the translocation of GLUT4 which was mediated by insulin signaling pathway repairment due to decreased expression of RETN and enhanced phosphorylation of IRS and Akt in GDM mice.

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and one of the main global health issues in which liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Owing to the link between NAFLD and insulin resistance (IR) and obesity and the role of resistin in theses metabolic disorders, we explored the possible association between resistin gene (RETN) variant and NAFLD. Methods A total of 308 unrelated subjects, including 152 patients with biopsy-proven NAFLD and 156 controls were enrolled and genotyped for the RETN gene rs3745367 variant using PCR-RFLP method. Results NAFLD patients had higher liver enzymes, systolic blood pressure (SBP), and diastolic blood pressure (DBP) than the controls (P

Background: Evidence suggests that circulating resistin levels are altered in colorectal cancer (CRC) and breast cancer (BC). Again, polymorphisms in resistin-encoding gene RETN have been evaluated in CRC and BC. However, there is a scarcity of data establishing the relationship of resistin and RETN polymorphisms (rs1862513 and rs3745367) with these cancers. This study aimed to analyze the relationship of resistin levels and RETN polymorphisms with CRC and BC in a combined meta-analytic approach. After a comprehensive online literature search, screening and eligibility check, 41 articles (31 with resistin level and 10 with RETN polymorphisms) were retrieved for meta-analyses. The mean difference (MD) of resistin was calculated and pooled to investigate the effect sizes with a 95% confidence interval (CI), and the connection of genetic polymorphisms was analyzed with an odds ratio (OR) and 95% CI. The analysis showed that resistin level is significantly higher in CRC (MD = 3.39) and BC (MD = 3.91) patients. Subgroup analysis in CRC showed significantly higher resistin in serum (MD = 4.61) and plasma (MD = 0.34), and in BC, a significantly elevated resistin level was reported in premenopausal (MD = 7.82) and postmenopausal (MD = 0.37) patients. Again, RETN rs1862513 showed a significantly strong association with CRC (codominant 1—OR 1.24, codominant 2—OR 1.31, dominant model—OR 1.25, and allele model—OR 1.16) and with BC (codominant 2—OR 1.51, codominant 3—OR 1.51, recessive model—OR 1.51, and allele model—OR 1.21). RETN rs3745367 did not show any association with these cancers. Short conclusion: Overall, our analysis indicates that higher circulating resistin levels are associated with an elevated risk of CRC and premenopausal and postmenopausal BC. Besides, rs1862513 in RETN gene is significantly connected with both CRC and BC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is more common with 90% of malignant neoplasm in oral cavity. Multiple factors leading to OSCC like genetic alterations, chromic exposure, micro environmental carcinogens, premalignant disease like oral epithelial dysplasia, mitochondrial membrane damage and viruses infections like HPV (human papillomavirus). RETN gene belongs to the family of mouse resistin-like genes. Human genetic variations are found to influence inter-individual variation observed in disease susceptibilities, drug response, response to an infectious disease. At the molecular level these sequence variations influence gene expression, protein production, function, disease susceptibility in particular individuals. The present in silico study determines the possible association of RETN polymorphism with that of oral squamous cell carcinoma in different populations. In this study the RETN gene polymorphism rs321975 was analysed in comparison to the global frequencies. The present study attempts to identify the possible reason for the selection of "A" allele in the south asian population. Furthermore, genotyping analysis has to be performed in a south Indian population to ascertain the association between RETN polymorphism (rs3219175) and OSCC. [ABSTRACT FROM AUTHOR]

Abstract Background Alcohol‐induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol‐induced ONFH in Chinese Han population. Methods A case–control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RETN gene and four SNPs in LDLR gene were genotyped using Agena MassARRAY platform. In allele model and genetic model, chi‐square test and logistic regression were used to study the associations between these SNPs and ONFH susceptibility. In addition, the relationships between these SNPs, clinical phenotypes, and blood lipid level with one‐way analysis of variance were analyzed. Results In the allele model, rs7408174 and rs3745369 in RETN were associated with increased risk of alcohol‐induced ONFH, whereas rs34861192 and rs3219175 in RETN showed reduced risk of alcohol‐induced ONFH. In the genetic model, rs7408174 was associated with increased risk of alcohol‐induced ONFH in dominant model and log‐additive model. Rs3745369 showed an increased risk in codominant model, recessive model, and log‐additive model. Rs34861192 showed a decreased risk in codominant model, dominant model, and log‐additive model, and rs3219175 showed a decreased risk in dominant model and log‐additive model. The rs3745368 in RETN was associated with the clinical stage of the disease. Conclusion These results suggest that RETN genetic polymorphisms are associated with the susceptibility of alcohol‐induced ONFH in Chinese Han population.

Background: Breast cancer is the most common cancer in women worldwide. Approximately 70% of female breast cancer patients have a body mass index (BMI) >25. In obesity, adipose tissue secretes additional resistin, which prompts a proinflammatory effect through its action on adenylate cyclase-associated protein 1 (CAP1). Several studies have associated the RETN gene single nucleotide polymorphism (SNP) rs1862513 (-420CCAP1 gene SNP rs35749351 (missense, Arg294His), located in the extracellular domain, has not previously been studied in cancer. These two SNPs, the mRNA expression levels of the two alleles for each of the cognate genes, and the serum resistin levels were compared between patients and controls to determine their association with breast cancer in Mexican women in this study. Materials and Methods: This study included 308 controls and 100 female patients with breast cancer. SNPs were detected by PCR-RFLP from DNA isolated from peripheral blood. Gene expression was performed with hydrolysis probes in tumor tissue. Resistin levels were quantified from serum samples by ELISA. Results: The RETN rs1862513CG/GG and CAP1 rs35749351GA/AA genotypes were associated with 1.61 and 2.193-fold increased risks of breast cancer, respectively, compared with the CC and GG genotypes. Similarly, carriers of the G allele of rs1862513 and the A allele of rs35749351, had 1.51 and 2.217-fold increased risks of breast cancer compared with the C and G alleles, respectively. The rs1862513GG/rs35749351AA genotype combination increased breast cancer risk by twofold. Serum resistin levels in postmenopausal breast cancer women were higher compared with postmenopausal controls. Tissue CAP1 expression showed differences with regard to molecular subtypes and metastases. Conclusion: The RETN and CAP1 polymorphisms and gene expression may be potential biomarkers for breast cancer risk. [ABSTRACT FROM AUTHOR]

The genomics era has brought along the completed sequencing of a large number of bird genomes that cover a broad range of the avian phylogenetic tree (>30 orders), leading to major novel insights into avian biology and evolution. Among recent findings, the discovery that birds lack a large number of protein coding genes that are organized in highly conserved syntenic clusters in other vertebrates is very intriguing, given the physiological importance of many of these genes. A considerable number of them play prominent endocrine roles, suggesting that birds evolved compensatory genetic or physiological mechanisms that allowed them to survive and thrive in spite of these losses. While further studies are needed to establish the exact extent of avian gene losses, these findings point to birds as potentially highly relevant model organisms for exploring the genetic basis and possible therapeutic approaches for a wide range of endocrine functions and disorders. [ABSTRACT FROM AUTHOR]

Visfatin and resistin appear to interfere with reproduction in the gonads, but their potential action at the hypothalamic-pituitary level is not yet known. The aim of the present study was to investigate the mRNA and protein expression of these adipokines in murine gonadotroph cells and to analyse the effects of different concentrations of recombinant mouse visfatin and resistin (0.01, 0.1, 1 and 10 ngmL-1) on LH secretion and signalling pathways in LβT2 cells and/or in primary female mouse pituitary cells. Both visfatin and resistin mRNA and protein were found in vivo in gonadotroph cells. In contrast with resistin, the primary tissue source of visfatin in the mouse was the skeletal muscle, and not adipose tissue. Visfatin and resistin both decreased LH secretion from LβT2 cells after 24 h exposure of cells (P<0.03). These results were confirmed for resistin in primary cell culture (P<0.05). Both visfatin (1 ngmL-1) and resistin (1 ngmL-1) increased AMP-activated protein kinase a phosphorylation in LβT2 cells after 5 or 10 min treatment, up to 60 min (P<0.04). Extracellular signal-regulated kinase α phosphorylation was transiently increased only after 5 min resistin (1 ngmL-1) treatment (P<0.01). In conclusion, visfatin and resistin are expressed in gonadotroph cells and they may affect mouse female fertility by regulating LH secretion at the level of the pituitary. [ABSTRACT FROM AUTHOR]

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.

Obesity is an emerging health problem in purebred dogs. Due to their crucial role in energy homeostasis control, genes encoding adipokines are considered candidate genes, and their variants may be associated with predisposition to obesity. Searching for polymorphism was carried out in three adipokine genes (TNF, RETN and IL6). The study was performed on 260 dogs, including lean (n = 109), overweight (n = 88) and obese (n = 63) dogs. The largest cohort was represented by Labrador Retrievers (n = 136). Altogether, 24 novel polymorphisms were identified: 12 in TNF (including one missense SNP), eight in RETN (including one missense SNP) and four in IL6. Distributions of five common SNPs (two in TNF, two in RETN and one in IL6) were further analyzed with regard to body condition score. Two SNPs in the non-coding parts of TNF (c.-40A>C and c.233+14G>A) were associated with obesity in Labrador dogs. The obtained results showed that the studied adipokine genes are highly polymorphic and two polymorphisms in the TNF gene may be considered as markers predisposing Labrador dogs to obesity. [ABSTRACT FROM AUTHOR]

• The resistin gene was positively correlated with tumor necrosis factor-alpha. • rs3219177 polymorphism and male sex were positively associated with the treatment. • This study trained various prediction models and provided insights into treatment. This study was designed to investigate the effects of polymorphisms in RETN on remission in RA patients receiving TNF-α inhibitors. In addition, machine learning algorithms were trained to predict remission. Ten single-nucleotide polymorphisms were investigated. Univariate and multivariable analyses were performed to evaluate associations between genetic polymorphisms and the efficacy of TNF-α inhibitors. A random forest–based classification approach was used to assess the importance of different variables associated with the efficacy of TNF-α inhibitors. Various machine learning methods were used for finding vital factors and prediction of remission. The eight most significant features included in the multivariable analysis were sex, age, hypertension, sulfasalazine, rs1862513, rs3219178, rs3219177, and rs3745369. T-allele carriers of rs3219177 and males showed approximately 6.0- and 3.6-fold higher remission rates compared to those with the CC genotype and females, respectively. The elastic net algorithm was the best machine-learning method for predicting remission of patients with RA treated with TNF-α inhibitors. On the basis of the results of this study, it may be possible to design individually tailored treatment regimens to predict the efficacy of TNF-α inhibitors. [ABSTRACT FROM AUTHOR]

Background: Resistin (Retn) is a cytokine which has a controversial physiological role regarding its involvement with obesity and type II diabetes mellitus. Recently, murine Retn was found to be a possibly potential regulator of hematopoiesis in mice shown in the screening results of a set of gene chips which mapped the expression level of murine genes during regeneration of impaired bone marrow (BM) by 5-fluorouracil. Results: Recombinant mice Retn was expressed in Escherichia coli and purified using ion exchange chromatography. Totally 11.4 mg rmRetn was obtained from 500 ml culture with endotoxin level less than 1.0 EU/ug. The purity of recombinant murine Resistin reached to at least 97.6 % via SDS-PAGE analysis and HPLC. The protein possessed chemotaxis effects in the mouse aortic endothelial cells in vitro in transwell analysis. In vitro, rmRetn could up regulate the CFU number of mice BM and after rmRetn was administered, the cell number of murine bone marrow was significantly increased in vivo after chemotherapy. Finally, rmRetn was found able to protect mice from the chemotoxicity of 5-fluorouracil. Conclusions: The discovery demonstrated a new function of murine Retn and suggested that it could potentially accelerate bone marrow regeneration post chemotherapy. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNP) in the resistin gene ( RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers. [ABSTRACT FROM AUTHOR]

Background: The published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research., Methods: PubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0., Results: A total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87-1.10, p heterogeneity <.001; I 2 = 84.6%; for the dominant model: OR = 0.96, 95% CI = 0.80-1.15, p heterogeneity <.001; I 2 = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; p heterogeneity <.001; I 2 = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; p heterogeneity <.001; I 2 = 80.9%)] and decreased risk in older people [for dominant: OR = 3.14 (95% CI, 2.35-4.19; p heterogeneity = .98; I 2 = 0.0%)]., Conclusions: Current results found no evidence that the RETN -420C/G variant was linked to T2DM susceptibility, but the patient's age appears to be a potential factor that contributed to high heterogeneity across studies. Additional high-quality and well-designed investigations are required to confirm these results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Shi, Guo, Cheng, Xu, Zeng, Huang, Huang, Wei, Wang, Chen and Ma.)

Abstract: Searching for effects of candidate gene polymorphisms on fatness traits is an important goal for pig industry. In this study we evaluated polymorphism of four porcine genes involved in energy metabolism (RETN, UCP1, UCP3 and ADRB3). Moreover, their association with fat deposition traits was analyzed in two breeds (Polish Landrace, Polish Large White) and a Polish synthetic line (L990). Altogether, five SNPs were identified, including two novel ones in the 5′-flanking region of the RETN gene and a novel missense substitution in the UCP3. Distribution of these polymorphisms in the studied five breeds and the synthetic line was not uniform. Two of the analyzed SNPs: g.−178G>A in the RETN and g.946C>T in the UCP3 gene revealed a significant association with abdominal fat weight or backfat thickness. Such associations were not observed for the UCP1 or ADRB3 gene polymorphisms. Our study showed that polymorphisms of the UCP3 and RETN genes are potentially associated with porcine fatness traits. [Copyright &y& Elsevier]

Abstract: The ARID is an ancient DNA-binding domain that is conserved throughout the evolution of higher eukaryotes. The ARID consensus sequence spans about 100 amino acid residues, and structural studies identify the major groove contact site as a modified helix-turn-helix motif. ARID-containing proteins exhibit a range of cellular functions, including participation in chromatin remodeling, and regulation of gene expression during cell growth, differentiation, and development. A subset of ARID family proteins binds DNA specifically at AT-rich sites; the remainder bind DNA nonspecifically. Orthologs to each of the seven distinct subfamilies of mammalian ARID-containing proteins are found in insect genomes, indicating the minimum age for the organization of these higher metazoan subfamilies. Many of these ancestral genes were duplicated and fixed over time to yield the 15 ARID-containing genes that are found in the human, mouse, and dog genomes. This paper describes a nomenclature, recommended by the Mouse Genomic Nomenclature Committee (MGNC) and accepted by the Human Genome Organization (HUGO) Gene Nomenclature Committee, for these mammalian ARID-containing genes that reflects this evolutionary history. [Copyright &y& Elsevier]

Background: Gene polymorphism is an important factor affecting the efficacy and dosage of opioids. A recent study showed RETN rs3745367 was associated with postoperative pain intensity. OPRM1 gene was confirmed to affect the postoperative analgesic consumption of morphine and other opioids., Objective: In this study, we investigated the association between single nucleotide polymorphisms (SNPs) in the RETN, OPRM1 gene and postoperative pain intensity, analgesics consumption, and ADR. The haplotype analysis focus on OPRM1 was also implemented., Study Design: This was a prospective, observational study., Setting: Patients undergoing spinal fusion and correction operation were recruited. Genotypes of rs3745367, rs1799971, rs2075572, and rs9322447 were tested. Pain assessment was performed to measure postoperative pain intensity, postoperative fentanyl and pethidine consumption was recorded to calculate analgesics consumption, and adverse reactions were recorded., Method: We recruited 142 patients undergoing spinal correction and fusion. Genotyping was performed by using a real-time polymerase chain reactions (PCRs) system and validated with allelic discrimination assays. The pain was assessed using a numerical rating scale (NRS). Statistical analyses were performed using SPSS software. LD test and the construction and analysis of haplotype were using Haploview software., Results: Rs3745367 demonstrated a significant association with postoperative average pain intensity in 24h (P = 0.015) and 48h (P = 0.001) after surgery. Rs2075572 and rs9322447 influenced postoperative maximal pain intensity in 48h after surgery (P = 0.042, 0.033, respectively). No correlation was found between OPRM1 SNPs and analgesics consumption and adverse reaction. According to the results of this study, a strong LD was observed between rs1799971 and rs9322447 (Block 1, LD parameters: D' = 0.82, r2 = 0.14), rs2075572 and rs9322447 (Block 2, LD parameters: D' = 0.92, r2 = 0.51)., Limitations: The association between rs3745367 with serum resistin levels was not investigated in this research, serum resistin levels of the incision part should be investigated in future studies., Conclusion: RETN rs3745367 was associated with postoperative average pain intensity, OPRM1 rs2075572 and rs9322447 may influence postoperative maximal pain intensity.

Copper toxicosis is a complex genetic disorder in Labrador retrievers characterized by hepatic copper accumulation eventually leading to liver cirrhosis. The variation of hepatic copper levels in Labrador retrievers has been partly explained by mutations in ATP7A c.980C>T and ATP7B c.4358G>A. To further elucidate the genetic background of this disease, we used targeted Next Generation Sequencing (NGS) in a cohort of 95 Labrador retrievers to analyze 72 potential modifier genes for variations associated with hepatic copper levels. Variants associated with copper levels were subsequently evaluated in a replication cohort of 144 Labrador retrievers. A total of 44 variants in 25 different genes were identified, of which four showed significant association with copper levels. Of the four variants found associated with hepatic copper levels in the NGS cohort, one was validated in the replication cohort. The non-reference allele of the variant NC&#95;006602.3.g.52434480C>T in RETN resulting in amino-acid change p.Leu7Phe was associated with decreased hepatic copper levels. In humans, resistin is associated with severity of non-alcoholic fatty liver disease, fibrosis, cirrhosis and mitochondrial dysfunction in hepatocytes. Further studies are needed to investigate the biological function of RETN p.Leu7Phe in the development of copper toxicosis in Labrador retrievers.

Background: Alcohol‐induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol‐induced ONFH in Chinese Han population. Methods: A case–control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RETN gene and four SNPs in LDLR gene were genotyped using Agena MassARRAY platform. In allele model and genetic model, chi‐square test and logistic regression were used to study the associations between these SNPs and ONFH susceptibility. In addition, the relationships between these SNPs, clinical phenotypes, and blood lipid level with one‐way analysis of variance were analyzed. Results: In the allele model, rs7408174 and rs3745369 in RETN were associated with increased risk of alcohol‐induced ONFH, whereas rs34861192 and rs3219175 in RETN showed reduced risk of alcohol‐induced ONFH. In the genetic model, rs7408174 was associated with increased risk of alcohol‐induced ONFH in dominant model and log‐additive model. Rs3745369 showed an increased risk in codominant model, recessive model, and log‐additive model. Rs34861192 showed a decreased risk in codominant model, dominant model, and log‐additive model, and rs3219175 showed a decreased risk in dominant model and log‐additive model. The rs3745368 in RETN was associated with the clinical stage of the disease. Conclusion: These results suggest that RETN genetic polymorphisms are associated with the susceptibility of alcohol‐induced ONFH in Chinese Han population. [ABSTRACT FROM AUTHOR]

The present study aimed to assess any associations between resistin gene (RETN) polymorphisms and cancer susceptibility by conducting a meta-analysis. A comprehensive literature search was performed with PubMed, Web of Science, Scopus and Google Scholar for relevant studies published before April 2018. For the rs1862513 polymorphism, data from 9 studies covering 1,951 cancer patients and 2,295 healthy controls were included in this meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Our meta-analysis revealed that this RETN polymorphism significantly increased the risk of cancer in codominant (OR=1.23, 95% CI= 1.01-1.50, p=0.04, CG vs CC; and OR=1.25, 95% CI= 1.03-1.53, p=0.03, GG vs CC), dominant (OR=1.19, 95% CI= 1.05-1.35, p=0.006, CG+GG vs CC), and allele (OR=1.14, 95% CI= 1.00-1.30, p=0.04, G vs C) inheritance genetic models. Stratification analysis by cancer type revealed that the rs1862513 variant significantly increased the risk of colorectal and breast cancer, and that cancer overall in Caucasians (OR=1.22, 95% CI= 1.04-1.43, p=0.02, CG+GG vs CC; OR=1.18, 95% CI= 1.04-1.34, p=0.01, G vs C). The data revealed no correlation between the rs3745367 polymorphism and cancer risk. Further well-designed studies with larger sample sizes and different ethnicities are warranted to validate the present findings., (Creative Commons Attribution License)

Background/aim: Adipocyte gene expression is altered in obese individuals through multiple metabolic and biochemical pathways. In this study, we aimed to examine the expression of resistin (Retn), amylin (Iapp), and dopamine receptor domain 5 (Drd5) genes previously suggested to contribute to the pathogenesis of obesity, albeit controversially. We also aimed to determine the effects on short and long-term mRNA levels of these genes in obese mice, induced with high-fat diet (HFD)., Materials and Methods: Two obesity models were created in our study: group T1 (20 mice) was fed with HFD (60% fat) for 3 months, and group T2 (20 mice) was fed with HFD (60% fat) for 6 months. The control group T0 (20 mice) was fed with a diet of 10% kcal fat supplement for 6 months. At the end of the experiment, their adipose tissues were dissected surgically. Tissue samples of each group were pooled for RNA isolation, cDNA synthesis was carried out and the mRNA levels were examined by quantitative real-time polymerase chain reaction. Serum resistin levels were measured using multiplex bead (luminex) technology for validation., Results: In T2 mice, the mRNA expression of Retn showed a moderate up-regulation (fold change=8.32; p=0.0019) in the adipose tissues. Iapp expression was also significantly up-regulated (fold change=9.78; p=0.012). Moreover, a 6.36-fold up-regulation for Drd5 was observed in the adipose tissues of T2 mice (p<0.001). At the same time, serum levels of resistin were found to be high in T1 and T2 mice compared to the control group (p<0.001 and p=0.024, respectively)., Conclusion: Our study demonstrated that the mRNA levels of the genetic markers considered to play a role in adipogenesis were different in short- and long-term obesity models formed in C57BL/6J mice using HFD., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Adipose tissue is an important endocrine organ that secretes a number of adipokines, such as adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) which may be implicated in obesity. Some adipokines' polymorphisms of genes might influence their concentrations and/or activities. Our aim was to study the relationship between seven SNPs in ADIPOQ (+45T

Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT(-/-)) mice, which cannot form atoxic Cd-MT complexes and are used for evaluating Cd as free ions, and wild type (MT(+/+)) mice. Cd administration more significantly reduced the adipocyte size of MT(-/-) mice than that of MT(+/+) mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT(-/-) mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes., (© 2013. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between the resistin intronic +299G/A polymorphism and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM)., Methods: We selected 738 T2DM patients, including 395 with NAFLD and 343 without fatty liver disease, as well as 279 healthy control individuals, and analyzed their resistin +299G/A polymorphism genotype by polymerase chain reaction-restriction fragment length polymorphism., Results: Plasma resistin levels in T2DM patients with NAFLD were at the highest (P<0.05). The frequency of AA genotype at the +299 site of the resistin gene in patients with concurrent T2DM combined with NAFLD was significantly different from that in the control (P<0.05). The AA genotype was found to be associated with a 1.80-fold increased risk for T2DM combined with NAFLD, 2.05-fold increased risk for obesity and 2.37-fold increased risk for obesity of abdominal type compared to the GG (P<0.05, respectively). The multivariate non-conditional logistic regression model analysis further shows that the AA genotype is a risk factor for the development of NAFLD in T2DM patients (OR, 2.32; 95% CI, 1.05-4.68; P<0.05)., Conclusion: The resistin +299AA genotype may be associated with increases in the risk of the NAFLD development in T2DM patients., (© 2013 Elsevier B.V. All rights reserved.)

Background and Objective: The polymorphism of the resistin gene (RETN/RSTN) has been associated with metabolic alterations. In this study the association between the 3'UTR +62G>A polymorphism and metabolic syndrome components was evaluated., Subjects and Methods: The population (n=218) was distributed in 3 groups: the control group with no metabolic alterations (n=77), nSMA group with isolated metabolic alterations (n=94) and MS group with metabolic syndrome (n=47). The 3'UTR +62G>A polymorphism was analyzed by PCR-RFLP., Results: Central obesity was the most frequent alteration in both nSMA (56.4%) and MS (91.5%) groups followed by low c-HDL levels in the nSMA group (42.6%) and arterial hypertension in the MS group (85%). The frequency of the +62G/A genotype was 20.2% in the population. The G/A genotype was more frequently found in the MS (38.3%) and nSMA (17%) groups than in the control group (13%). The allelic distribution between the control group (+62G=0.94, +62A=0.06) and MS group (+62G=0.81, +62A=0.19) was significantly different (P=.0001). Significant associations between the G/A genotype and high values of abdominal circumference (P=.047), basal glycemia (P=.02) and systolic arterial pressure (P=.003) were found., Conclusion: The findings suggest the association between the G/A genotype and high values of systolic arterial pressure, basal glycemia and abdominal circumference. This association was independent of the metabolic syndrome context., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.

This study's objective was to examine the associations between resistin (RETN) polymorphisms, plasma resistin levels, and type 2 diabetes risk. We conducted two nested case-control studies in postmenopausal women (359 incident cases and 359 controls) and middle-aged/elderly men (170 incident cases and 170 controls). Controls were matched (1:1) to cases by age, race, duration of follow-up, and time of blood draw. Circulating resistin levels were higher among carriers of the variant allele for rs34861192 (p<0.0001 for women, p=0.002 for men) but not rs1862513 (p=0.15 for women, p=0.14 for men). Neither polymorphism was significantly associated with risk of type 2 diabetes after adjusting for diabetes risk factors (exercise, smoking status, alcohol intake, family history of diabetes, and matching factors) among women (rs1862513: OR=1.19, 95% CI=0.80-1.77; rs34861192: OR=0.41, 95% CI=0.14-1.19) and men (rs1862513: OR=1.05, 95% CI=0.57-1.95; rs34861192: OR=0.64, 95% CI=0.14-2.89). In conclusion, RETN promoter polymorphism rs34861192 was associated with elevated circulating resistin levels, but rs1862513 was not. Neither polymorphism was associated with an increased risk for type 2 diabetes.