GENETIC VARIANTS IN LIPID-ASSOCIATED GENES IN THE KAZAKHSTANI COHORT WITH ATHEROSCLEROSIS AND HYPERTRIGLYCERIDEMIA
Introduction. Cardiovascular diseases, including atherosclerosis (AS), are the leading cause of morbidity and mortality worldwide, including in Kazakhstan. Lipid metabolism disorders, in particular, hypertriglyceridemia, which is recognized as an independent risk factor, play an important role in the development of AS. Genetic features associated with genes regulating lipid and carbohydrate metabolism (GCKR, SLC22A5, LPL, FLCN, LDLR, APOE) have a significant impact on the formation of dyslipidemia and determine individual metabolic characteristics. Studying the prevalence and effects of these genetic variants in the Kazakh population is particularly important, given its underrepresentation in global genetic research.
Aim. The objective of this study was to study the frequency of genetic polymorphisms in genes involved in the regulation of lipid metabolism (GCKR, SLC22A5, LPL, FLCN, LDLR, APOE) in a group of Kazakhstani patients with hypertriglyceridemia and atherosclerosis. Additionally, we analyzed the relationship of the identified genetic variants with the biochemical parameters of the lipid profile.
Materials and methods. The study analyzed data from 402 patients with cardiovascular diseases, 144 of whom had hypertriglyceridemia. To identify the genetic determinants of lipid metabolism disorders, full-exome sequencing was performed with a focus analysis of the GCKR, SLC22A5, LPL, and FLCN genes. The identified genetic variants were annotated and classified according to the recommendations of ACMG/AMP. The association of genetic polymorphisms with lipid profile parameters in patients with AS was studied.
Results. Sequencing of the entire exome of patients with varying degrees of cardiovascular risk revealed genetic variations affecting triglyceride metabolism. Elevated triglyceride levels were reported in patients of all risk categories, with the highest frequency in very high-risk individuals (82 patients). Analysis of the lipid profile showed that total cholesterol was significantly higher in the high-risk group compared with the low-risk group (228.8±35.2 versus 207.8±30.3 mg/dl; p=0.0467). The level of HDL-C showed an inverse relationship with the level of risk, being the lowest in the very high-risk group (44.6±10.5 versus 50.1±9.9 mg/dl; p=0.0411). Although LDL and non-lipoprotein cholesterol did not show statistically significant differences, there was a tendency to increase them. Triglycerides also tended to increase, but without achieving statistical significance (p>0.05). There was a significant decrease in apolipoprotein A at high risk (p<0.0001). The distribution of APOE genotypes (p.T388C) was similar in all risk groups, with a predominance of the TT genotype (≈58-67%) and a rare occurrence of the CC genotype (≤5.3%), without statistically significant differences (p>0.05).
Conclusions. The study did not reveal a statistically significant association between APOE (p.T388C) and GCKR genotypes with cardiovascular risk. Larger-scale studies are required, taking into account additional factors and an increased sample size.
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Bekbossynova M.S., Mirmanova Zh.Zh., Shakhmarova T.K., Chamoieva A.E., Zhalbinova M.R., Satvaldina N.N., Yerezhepov D.A., Rakhimova S.E., Kairov U.E., Daniyarov A.Zh., Ivanova-Razumova T.V., Andossova S.A., Sailybayeva A.I., Khamitov S.R., Akilzhanova A.R. Genetic variants in lipid-associated genes in the Kazakhstani cohort with atherosclerosis and hypertriglyceridemia // Nauka i Zdravookhranenie [Science & Healthcare]. 2025. Vol.27 (5), pp. 7-15. doi 10.34689/SH.2025.27.5.001Похожие публикации:
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