Adiponectin is encoded by the ADIPOQ gene and participates in the pathogenesis of cardiovascular and metabolic diseases. The goal of the study was to assess associations of rs17300539, rs266729, rs182052, rs2241766, and rs17366743 single nucleotide polymorphisms (SNPs) of the ADIPOQ gene with concentrations of serum adiponectin and with coronary atherosclerosis and type 2 diabetes mellitus in 447 patients (316 men and 131 women) subjected to coronary angiography. SNPs of the ADIPOQ gene of the study participants were genotyped using real-time PCR. Multivariate linear regression adjusted for covariates revealed significant association between rs182052 SNP and serum adiponectin concentration (β= –0.11; 95% confidence interval (95%CI): –0.19, –0.03; p = 0.016). Regression analysis revealed an increase in prevalence of unstable angina (OR (odds ratio) = 2.55; 95%CI 1.4–4.82; p = 0.018) and coronary artery disease (OR = 1.55; 95%CI 1.15–2.09; p = 0.021) per copy of the rs182052 A allele. Prevalence of type 2 diabetes mellitus was higher in subjects with the rs182052 A allele (OR = 2.29; 95%CI 1.29-4.21; p = 0.024). Regression analysis of rs266729 showed that prevalence of unstable angina was increased (OR = 3.59; 95%CI 1.17–10.01; p = 0.045) in the subjects with the GG genotype and prevalence of coronary artery disease (CAD) was significantly increased (OR = 1.48; 95%CI 1.09–2.03; p = 0.045) per copy of the G allele. Haplotype analysis revealed that the subjects with the GCATT haplotype have lower adiponectin levels (β= –0.15; p = 0.042) and higher prevalence of unstable angina (OR = 3.597; p = 0.007) compared with reference haplotype carriers. Thus, the results indicate that minor A allele of rs182052 of the ADIPOQ gene is significantly associated with a decrease in serum adiponectin levels, and two SNPs (rs182052 and rs266729) of the ADIPOQ gene are significantly associated with cardiovascular and metabolic diseases.

Aim. To study the contribution of rare and low-frequency variants of ANGPTL3, ANGPTL4, APOA5, APOB, APOC2, APOC3, LDLR, PCSK9, LPL genes in assessing the risk of coronary artery disease (CAD) in a cohort of Russian patients with various cardiovascular risks.Material and methods. The study was conducted on a sample of participants in cohort and epidemiological studies (n=2405). Targeted enrichment of coding sequences and exon-intron regions of nine genes (ANGPTL3, ANGPTL4, APOA5, APOB, APOC2, APOC3, LDLR, PCSK9, LPL) was performed. Genetic diagnostics was carried out by next generation sequencing.Results. CAD was confirmed in 267 patients (11%). After genetic diagnosis, all patients were divided into three following groups: individuals with previously described genetic variants associated with elevated levels of low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TGs); individuals with genetic variants associated with reduced levels of LDL-C and/or TGs; individuals without genetic variants associated with LDL-C and/or TG levels, or with two or more variants with opposite effects on LDL-C and/or TG levels. Kaplan-Meier method revealed that the groups significantly differ in cumulative risk of CAD (p<0,001 for the log-rank test), the maximum risk was in group 1, and the minimum risk in group 2. When conducting the Cox regression, we found that in persons from group 1, the hazard ratio (HR) for CAD is 2,63 times higher (HR =2,63, 95% confidence interval (CI), 1,6-4,34; p<0,001), and in persons from group 2 lower by 1,88 times (HR =0,53, 95% CI, 0,3-0,98; p=0,042) compared with persons from group 3, adjusted for other CAD risk factors: sex, age, smoking, LDL-C and hypertension.Conclusion. Genetic testing in young patients makes it possible to identify individuals with an increased genetic risk of CAD and to focus preventive and therapeutic measures primarily for this category of patients.

Adiponectin, endothelin and nitric oxide (NO) are major regulators of vascular function. An imbalance of vasoactive factors contributes to the onset and progression of atherosclerosis. Various single nucleotide polymorphisms (SNPs) are considered to be risk factors for coronary heart disease. However, the molecular mechanisms of their associations with the components of endothelial dysfunction are poorly understood. In the present study, rs17366743, rs17300539, rs266729, rs182052 and rs2241766 SNPs of the adiponectin (ADIPOQ) gene and rs2070699, rs1800542 and rs1800543 SNPs of the endothelin‑1 (EDN1) gene were genotyped in 477 patients with coronary heart disease who were subjected to coronary angiography, in order to determine the presence or absence of coronary atherosclerosis. The serum levels of adiponectin, endothelin and stable metabolites of NO, (nitrate and nitrite NOx), were assayed and their associations with the SNP genotypes and coronary lesions were calculated. The results indicated that rs17366743 of the ADIPOQ gene and rs2070699 and rs1800543 of the EDN1 gene were associated with the levels of NOx in women, which in turn was associated with cardiovascular mortality. In men, rs182052 and rs266729 of the ADIPOQ gene were associated with adiponectin levels, whereas rs17366743 of the ADIPOQ gene was associated with endothelin levels. Additionally, these SNPs were indirectly associated with the prevalence of coronary lesions in men. Therefore, the tested SNPs can be considered potential risk factors that lead to imbalance of vasoactive mediators in a gender‑specific manner and contribute to the development of clinical manifestations of atherosclerosis.