Associations of rs2305948 and rs1870377 polymorphic variants of the vascular endothelial growth factor receptor type 2 (KDR) gene with the risk of coronary heart disease
Background: According to statistics, the first place among the causes of death worldwide is occupied by cardiovascular diseases (CVD), of which a large proportion are cases of coronary heart disease (CHD). In this regard, to date, research is actively being conducted to study its previously unknown etiological aspects. Especially relevant in modern conditions is the search for genetic markers of the disease, potentially applicable in the future for the early diagnosis of CHD, as well as the establishment of a hereditary predisposition to it. The aim of the study: To study the association of polymorphic variants of rs2305948 and rs1870377 of the KDR gene with the risk of CHD in Central Russia. Materials and methods: The study included 1390 DNA samples: 635 CHD patients and 755 healthy people. DNA was isolated by phenol-chloroform extraction. Genotyping of DNA polymorphisms was performed using real-time PCR with allele discrimination using TaqMan probes. We used the CFX96 amplifier and Applied Biosystems kits. Statistical processing of results was carried out using the resources of the SNPstats program. We performed functional annotation of SNPs on the basis of available bioinformatic resources. Results: We found that there is sexual dimorphism in relation to KDR with the development of CHD. We found a statistically significant Association of the a/T rs1870377 genotype of the VDR gene with the risk of CHD in men. Bioinformatic analysis revealed the relationship of rs1870377 polymorphism with increased expression of the SRD5A gene (an enzyme that converts testosterone to dihydrotestosterone), which may be one of the reasons for gender differences in studying the risk of CHD in this particular case. Conclusion: For the first time in the Russian population, the study examined the relationship of polymorphic variants of the KDR gene with the risk of CHD. It was found that the rs1870377 polymorphism of the KDR gene is statistically significantly associated with risk of CHD in males.