Genetic risk factors for restenosis after percutaneous coronary intervention in Kazakh population.

BACKGROUND: After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population. METHODS: Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2. RESULTS: A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR = 2.924, P = 2.3E-06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR = 0.08033, P = 2.11E-09) and dominant models (OR = 0.05359, P = 4.15E-11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR = 20.05, P = 2.74 E-12) and recessive models (OR = 22.24, P = 6.811E-10). CONCLUSIONS: Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.

Genetic markers of the risk of coronary heart disease and coronary artery thrombosis developing in the Kazakh population.

Background: Surgical methods such as coronary artery bypass grafting and percutaneous coronary interventions (PCI) are widely used along with traditional conservative therapy in the treatment of coronary artery disease. The disease outcome directly depends on timely diagnosis and treatment. A significant role in predicting the effectiveness of treatment is given to personification of treatment and management of the patient. In this case, the determining component is its individual genetic status. Methods: The study groups included persons of Kazakh nationality which identify themselves, their biological parents, and biological grandparents on the maternal and paternal side as Kazakh. Research groups included 108 people at the age from 45 to 65 years of both sexes. Blood samples genotyping was carried out by PCR using highly specific TaqMan samples. Thermo Fisher cloud application was used for genotypes determining on the base of an automatic algorithm. Results: The article presents the results of the evaluation of gene polymorphisms associated with coronary artery restenosis in a population of Kazakh nationality. 3 SNPs were determined when searching for an association with stenting due to coronary artery thrombosis: rs7543130 (p=0.009324), rs6785930 (p=0.016858), rs7819412 (p=0.061325). Conclusion: Four polymorphisms associated with the risk of developing coronary heart disease were revealed during the study of polymorphisms among the people of the Kazakh population. Three SNPs were determined when searching for an association with stenting due to coronary artery thrombosis. It should be noted that the Bonferonni correction for multiple comparisons did not reveal significant polymorphisms associated with coronary artery disease, which requires further research with more quantity of samples.

Genetic Predictors of the Development of Complications after Coronary Stenting.

Due to the fact that there are scientific discussions about the significance of gene polymorphisms in the risk of developing cardiovascular complications after a percutaneous coronary intervention, it is of interest to evaluate the genetic predictors of the development of cardiovascular events. This study is a molecular genetic study. Association with the genes of biomarkers for inflammation and immune response increases the risk of cardiovascular events: rs1234313 (TNFSF4): (A/G, OR-4.57 (2.35-8.87), p ≤ 0.0001), (A/G-A/A, OR-3.14 (1.75-5.63), p ≤ 0.0001), and (A/G, OR = 4.01 (2.19-7.36), p ≤ 0.0001); rs3184504 (SH2D3); ATXN2: (C/T, OR-2.53 (1.28-5.01), T/T, OR-2.99 (1.13-7.92), p = 0.017)), (C/T-T/T, OR-2.61 (1.35-5.07), p = 0.000), and (OR-1.89 (1.15-3.09), p = 0.009)). According to the lipid metabolism biomarker genes, rs2943634: (A/C OR-2.57 (1.18-5.62), p = 0.013); according to the endothelial biomarker genes, rs2713604: (DNAJB8-AS1; GATA2): (C/T, OR-4.27 (2.35-7.76), p ≤ 0.0001), (C/T-C/C, OR-4.13 (2.31-7.40), p ≤ 0.0001), (OR-4.05 (2.24-7.30), p ≤ 0.0001), and (C/T, OR-3.46 (1.99-6.00), p ≤ 0.0001). The regression analysis found that in the presence of the rs2943634 gene polymorphism, the risk of late cardiovascular events increases by 4.007 times with 95% CI (1.502:10.692), p = 0.006. The genes of biomarkers for the risk of cardiovascular events are rs1234313(TNFSF4), rs3184504 (SH2D3; ATXN2), rs2943634, and rs2713604 (DNAJB8-AS1; GATA2). The only predictor of the development of new cardiovascular events was rs2943634, which belongs to the group of lipid metabolism biomarkers.

Association of four genetic variants with colorectal cancer in Kazakhstan population.

The study was conducted to search for polymorphisms located in the 10th chromosome associated with colorectal adenocarcinoma in representatives of the Kazakhstan population. Study was performed with 282 colorectal cancer (CRC) patients and 159 controls. Genotyping of SNPs was performed by QuantStudio 12K Flex PCR. For four significant SNPs inheritance model analysis was performed. Increasing risk of CRC was noted for rs10795668 in log-additive model (OR = 1.45, 95% CI: 1.05-1.99, p = 0.023); for rs1035209 in log-additive model (OR = 1.79, 95% CI: 1.18-2.72, p = 0.003); for rs11190164 in log-additive model (OR = 1.67, 95% CI: 1.17-2.38, p = 0.004). Decreasing risk of CRC was noted for rs10506868 in log-additive model (OR = 0.56, 95% CI: 0.37-0.85, p = 0.006). We detected SNPs that are associated with CRC risk in the Kazakhstan population.

Dynamic changes in purine catabolism in patients with acute coronary syndrome that underwent percutaneous coronary intervention.

BACKGROUND: Cardiovascular diseases are global problems. They are causes of death in about 43% of people worldwide and may become the most widespread reason of death by 2020. The prognosis is directly dependent to immediate diagnosis and on time treatment. Introduction of new biochemical markers as the early diagnosis of complications after coronary revascularization is very important in this period. Herein, we assayed the changes of purine catabolites in patients with acute coronary syndrome (ACS) before and after percutaneous coronary intervention (PCI) in comparison with control group. METHODS: Thirty five ACS patients (20 males and 15 females) were included (57±17 years old) in the study. The determination of intermediates of purine catabolism as guanine, hypoxanthine (GCS), adenine, xanthine (Kc) and uric acid (MK) were assayed before and 3 days after PCI. Conditionally, 35 healthy-matched persons were included in the control group. Purine catabolites were determined in plasma through the method of Oreshnikov E.V (2008). RESULTS: In ACS patients, prior to PCI, there was a tendency to increase the concentration of guanine (P=0.001), hypoxanthine (P=0.002) adenine (P=0.0003), xanthine (P=0.000003) and uric acid (P=-0.000001) relative to the upper limits of normal ranges. And on the third day after PCI, there was the second tendency to increase the levels of guanine (P=0.000001), hypoxanthine (P=0.000001) adenine (P=0.0000001), xanthine (P=0.000001) and uric acid (P=0.0000001) relative to upper limits of normal ranges. CONCLUSION: Increment of plasma purine catabolites can be a marker of inflammation and instability of coronary artery plaques and may be used as a restenosis marker in patients with history of PCI.