Genetic association between regulation of GTPase activity pathway and high-altitude essential hypertension among Chinese Tajiks

Objective To screen the single nucleotide polymorphism (SNP) loci and related genes that are significantly associated with essential hypertension among Chinese Tajiks by using exon sequencing and to reveal the unique essential hypertension related gene polymorphisms of the high-altitude minority. Methods A total of 62 Chinese Tajiks (26 in the control group and 36 in the hypertension group) from Tashkurgan County (in the east of Pamir Plateau), Kashgar, Xinjiang Uygur Autonomous Region, in July 2017 were recruited in this study. Their venous blood were collected for DNA extraction to make exon sequencing. According to the significant differences in allele frequency distribution between the 2 groups, the SNP loci associated with essential hypertension were screened out. Finally, after the currently known hypertension-related genes were removed, enrichment analysis was carried out on the remaining genes to find out the most significant enrichment pathway, and the obtained top 5 significantly related SNP loci were further analyzed with genetic association analysis. Results A total of 6 739 SNP loci with statistically significant differences in allele frequency distribution between the 2 groups were screened out, and these loci were located on 3 646 genes in total. The remaining genes were significantly enriched in the regulation of GTPase activity pathway after the removal of currently known hypertension-related genes[log10(P)=-4.06]. Among them, the significantly related SNP loci and their genes were rs17261772(RAB3GAP1), rs7319836(LRCH1), and rs868188(ARHGEF11). Conclusion Regulation of GTPase activity pathway may be involved in the progression of essential hypertension among Chinese Tajiks. The mutation of rs17261772, rs7319836 and rs868188 on this pathway may have an important influence on the risk of hypertension to the high-altitude minority.