Search

Patients with genetically-based hyperlipidemias exhibit a wide phenotypic variability. Investigation of clinical and biochemical features is important for identifying genetically-based hyperlipidemias, determining disease prognosis, and initiating timely treatment. We analyzed genetic data from 3374 samples and compared clinical data, lipid levels (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a)), frequency, age at onset of coronary heart disease (CHD), and the severity of carotid and femoral atherosclerosis (plaque number, maximum stenosis, total stenosis, maximum plaque height, and plaque score) among patients with familial hypercholesterolemia (FH), familial dysbetalipoproteinemia (FD), polygenic hypercholesterolemia (HCL), severe HCL, and those without lipid disorders (n = 324). FH patients exhibited the highest LDL-C (median 8.03 mmol/L, p < 0.001). FD patients had elevated triglyceride levels (median 4.10 mmol/L), lower LDL-C (median 3.57 mmol/L), and high-density lipoprotein cholesterol (median 1.03 mmol/L) compared to FH, polygenic HCL, and severe HCL, p < 0.05. FH and FD patients had similar early onset of CHD, with a median age of 44 and 40 years and comparable frequencies of 29.5% and 31.0%, respectively. They were more likely to develop CHD than subjects without lipid disorders (p = 0.042 and p < 0.001, respectively). Additionally, FH patients had higher a carotid plaque number, total carotid stenosis, and carotid plaque score. This study presents the first simultaneous comparison of clinical and biochemical features among FD, FH, polygenic, and severe HCL, along with the first comprehensive evaluation of carotid and femoral atherosclerosis ultrasound parameters in FD patients. The results highlight distinct phenotypic features unique to each hyperlipidemia analyzed and underscore FH and FD as the most atherogenic hyperlipidemias. [ABSTRACT FROM AUTHOR]

Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare APOE variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare APOE variants and FD. Genetic data from 4720 subjects were used to identify rare APOE variants and investigate their pathogenicity for autosomal dominant FD. We observed 24 variants in 86 unrelated probands. Most variants were unique (66.7%). Five identified APOE variants (p.Glu63ArgfsTer15, p.Gly145AlafsTer97, p.Lys164SerfsTer87, p.Arg154Cys, and p.Glu230Lys) are causal for autosomal dominant FD. One of them (p.Lys164SerfsTer87) was described for the first time. When we compared clinical data, it was found that carriers of pathogenic or likely pathogenic APOE variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, p = 0.034) and variants of uncertain significance (median 1.38 mmol/L, p = 0.036). For the first time, we estimated the expected prevalence of causal variants for autosomal dominant FD in the population sample: 0.27% (one in 619). Investigating the spectrum of APOE variants may advance our understanding of the genetic basis of FD and underscore the importance of APOE gene sequencing in patients with lipid metabolism disorders. [ABSTRACT FROM AUTHOR]

Background: The present study investigates the feasibility of using three previously published genome-wide association studies (GWAS) results on blood lipids to develop polygenic risk scores (PRS) for population samples from the European part of the Russian Federation. Methods: Two population samples were used in the study – one from the Ivanovo region (n = 1673) and one from the Vologda region (n = 817). We investigated three distinct approaches to PRS development: using the straightforward PRS approach with original effect sizes and fine-tuning with PRSice-2 and LDpred2. Results: In total, we constructed 56 PRS scales related to four lipid phenotypes: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglyceride levels. Compared with previous results for the Russian population, we achieved an additional R2 increase of 2–4%, depending on the approach and lipid phenotype studied. Overall, the R2 PRS estimates approached those described for other populations. We also evaluated the clinical utility of blood lipid PRS for predicting carotid and femoral artery atherosclerosis. Specifically, we found that PRS for total cholesterol, low-density lipoprotein cholesterol, and triglycerides were positively correlated with ultrasound parameters of carotid and femoral artery atherosclerosis (ρ = 0.09–0.13, p < 0.001), whereas PRS for high-density lipoprotein cholesterol were inversely correlated with the number of plaques in the femoral arteries (ρ = −0.08, p = 8.71 × 10 − 3 ). Conclusions: PRS fine-tuning using PRSice-2 add LDpred2 improves the performance of blood lipid PRS. Our study demonstrates the potential for further use of blood lipid PRS for prediction of atherosclerosis risk. [ABSTRACT FROM AUTHOR]

Introduction: One of the key stages of evaluating an edentulous ridge prior to dental implant placement is the analysis of neighboring anatomical structures such as canalis sinuosus (CS) with cone-beam computed tomography (CBCT). CBCT visualization has its own features, such as the change of slice thickness. The aim of the study was to analyze CS prevalence in relation to the slice thickness and CS diameter according to CBCT scans.Materials and Methods: In total, 100 CBCT scans of 39 males and 61 females in the age span of 46 to 81 years were retrospectively studied. Terminal alveolar part of CS was analyzed in Ez3D2009 (Vatech) software on panoramic and cross-sectional views with 0.5 mm, 1 mm, 3 mm, and 10 mm slice thicknesses. The prevalence was documented with regard to the diameter and slice thickness and was statistically compared in age and gender groups.Results: This CBCT study demonstrated 55.5% CS prevalence. There was no statistically significant difference in presence between age and gender groups regarding diameter as well as within different slice thickness. The study also showed the importance of the slice thickness choice for CS visualization: the best visualization was reached with 0.5 mm and 1 mm slice thicknesses. Visualization with 0.5 mm and 1 mm slice thicknesses was absolutely the same (55.5%). General CS prevalence with a 10 mm slice thickness (16.5%) was significantly lower (P < 0.05) than the prevalence with a 3 mm slice thickness (20.5%). The correlation between the slice thickness and a diameter more than 1.5 mm in size was not found.Conclusion: CBCT analysis showed that the highest CS prevalence was detected with the use of 0.5/1 mm slice thickness. As well, the higher CS diameter, the better is its visualization. [ABSTRACT FROM AUTHOR]