The Association Study Of Single Nucleotide Polymorphisms And Haplotypes Of TERT And VEGF Genes With Longevity In Xinjiang Uygur Population

Objective:To investigate the correlation of the single nucleotide polymorphisms and haplotypes of TERT and VEGF genes with longevity in XinJiang Uygur population. Methods:A case-control design was applied in this study. In brief, a total of 361 Uygur subjects were selected in the study including 112 individuals≥90 years old and 249 controls. The genomic DNA was extracted from all peripheral blood samples. Based on genotype data from the international HapMap project, the tagging single nucleotide polymorphisms (tSNPs) were selected and linkage disequilibrium values D'and r2 were calculated in the population using the Maximation likelihood method. Haplotype frequencies were estimated using Phase 2.0 software.The locus of TERT gene including rs2736098(SNP1), rs2736100(SNP2), rs2853676(SNP3), rs10069690(SNP4), rs4975605 (SNP5), rs2075786(SNP6), rs2736118(SNP7), rs2853691(SNP8) were genotyped by snapshot method and the haplotype distribution was estimated. The same way was used in testing the locus of VEGF gene including rs2146323 (SNP1), rs3024997 (SNP2), rs10434 (SNP3), while the relationship of single nucleotide polymorphisms and haplotypes with genetic susceptibility to longevity was investigated. Results:Section one. Systolic blood pressure (SBP), pulse pressure (PP) in longevity group were significantly higher than in control group, while height, weight and body mass index (BMI) were significantly lower than in control group (P<0.05). There was a significant difference in the level of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), creatinine, uic acid and triglyceride (TG) between longevity group and control group (P<0.05). The prevalence of hypercholesterolemia and hyperuricemia was higher and the prevalence of overweight, obesity and hypertriglyceridemia was lower in longevity group than in control group.There were no significant differences in diastolic blood pressure (DBP), pulse pressure index (PPI), fasting blood glucose (FBG) and the prevalence of hypertension and hyperglycemia between the two groups (P>0.05). Section two:1) Eight common SNPs of TERT gene were chosen to be tagging SNPs. All polymorphisms were in Hardy-weinberg equilibrium both in longevity and in control group. The frequencies of G and T allele of TERT SNP2 in longevity group were 62.1%,37.9% and 51.6%,48.4% in the control group. The frequencies of SNP2 genotypes of GG, GT and TT in longevity group were 36.6%,50.9%,12.5%and 24.9%,53.4%,21.7% in control group respectively. The distributions of TT genotype and T allele of SNP2 (SNP rs2736100) in longevity group were lower than in control group and P equals to 0.026,0.009. The SNP rs2736100 was significantly associated with longevity (TT versus GG:P=0.008, OR=0.392,95%CI: 0.193～0.796; GT+TT versus GG:P=0.023, OR=0.574,95%CI:0.355～0.928; T versus G: P=0.009, OR=0.652,95%CI:0.473-0.900); 2) The frequencies of T and C allele of TERT SNP6 in longevity group were 66.5%,33.5% and 56.2%,43.8% in the control group. The frequencies of SNP6 genotypes of TT, TC and CC in longevity group were 45.5%,42.0%, 12.5% and 34.9%,42.6%,22.5% in control group respectively. The distributions of CC genotype and C allele of SNP6 (SNP rs2075786) in longevity group were lower than in control group and P equals to 0.044,0.009. The SNP rs2075786 was significantly associated with longevity (CC versus TT:P=0.013, OR=0.426,95%CI:0.216～0.842; C versus T:P=0.009, OR=0.647,95%CI:0.465～0.899); 3) The haplotype analysis revealed that the frequency of Hap 1-AT was highest in both groups. The frequencies of Hap 1-AT, Hap3-GC were higher in longevity group than in control group while the frequency of Hap2-AC was lower in longevity group. There was no statistically significant difference. 4) PP and PPI in GT+TT genotype combination were markedly higher than in GG genotype of TERT SNP2 in longevity group, while PPI in TC+CC genotype was markedly higher than in TT genotype of TERT SNP6 in control group. Section three:1) Three common SNPs of VEGF gene were chosen to be tagging SNPs. All polymorphisms were in Hardy-weinberg equilibrium both in longevity and in control group. The frequencies of C and A allele of VEGF SNP1 in longevity group were 70.1%,29.9% and 62.3%,37.7% in the control group. The frequencies of SNP1 genotypes of CC, CA and AA in longevity group were 47.3%,45.5%,7.2% and 42.6%,39.3%,18.1% in control group respectively. The distributions of AA genotype and A allele of SNP1 (SNP rs2146323) in longevity group were lower than in control group and P equals to 0.025, 0.041. The SNP rs2146323 was significantly associated with longevity (AA versus CC: P=0.011,OR=0.356,95%CI:0.156～0.808; A versus C:P=0.041, OR=0.704,95%CI: 0.502～0.987); 2) The haplotype analysis revealed that the frequency of Hapl-CG was highest in both groups. The frequency of Hapl-CG was higher in longevity group than in control group, while the frequencies of Hap2-CA, Hap3-AG were lower in longevity group. There was no statistically significant difference.3) The level of PP in CA+AA genotype combination was markedly higher than in CC genotype of VEGF SNP1 in control group. Conclusion:Our study revealed that TERT gene rs2736100 and rs2075786 polymorphisms might be associated with longevity in Xinjiang Uygur population. TT genotype, T allele of rs2736100 and CC genotype, C allele of rs2075786 were the adverse factors of longevity. VEGF gene rs2146323 polymorphism might be associated with longevity. AA genotype and A allele were the adverse factors of longevity in Xinjiang Uygur population. rs2736100, rs2075786 and rs2146323 might be associated with longevity through impacts on vascular function.