Correlation Between Single Nucleotide Polymorphisms In Three Sites Of Klotho Gene And Coronary Heart Disease

Objective: To study the associations between coronary heart disease(CHD) and single nucleotide polymorphisms (SNPs) in three sites of Klothogene (G-395A, F352V and C370S), the allele and genotype frequencies ofthese SNPs were investigated in patients with CHD and healthy people inChongqing.Methods:317patients with CHD and301healthy controls wererandomly enrolled. Genomic DNA was extracted from the peripheralleukocytes. And the single allele specific primer PCR technique(SASP-PCR) was used to detect allele and genotype distributions of these three SNPs.Results:1. The frequencies of AA genotype of KL G-395A in CHD group andcontrol group were13.95%and7.310%, respectively. The difference wasstatistically significant (P<0.05).In sex stratification subgroup analysis, we found the frequency of AAgenotype in male patients was14.14%and that in the control was7.07%.There was significant difference between these two subgroups (P<0.05).The frequency of CC genotype of KL C370S in CHD group and was49.21%. The frequency of allele CC genotype of KL C370S in the controlgroup was30.43%. The difference was statistically significant (P<0.05).In the subgroup analysis, we found that the frequency of CC genotypein patients of male subgroup was51.83%. The frequency of CC genotype incontrols of male subgroup was30.43%. The difference was also statisticallysignificant between these two groups (P<0.05).The frequency of CS genotype of KL C370S in CHD group was47.95%. The frequency of allele CS genotype of KL G370S in the controlgroup was62.13%. The difference was statistically significant (P<0.05).In the subgroup analysis, we found that the frequency of CS genotype inpatients of male subgroup was47.95%.The frequency of AA genotype in thecontrols of male subgroup was62.13%. The difference was statisticallysignificant between these two groups (P<0.05). We did not find statistically difference in the genotype distributions ofFF, FV and VV between CHD group and control group (P>0.05).2. According to the combination genotype analysis, this study indicatedthat the frequencies of KL G-395A+F352V+C370C, KL A-395A+F352V+C370C and KL A-395A+F352V+C370S in the CHD group were higher thanthat in the control group (P<0.05). But the frequency of KLG-395A+F352V+C370S was lower than that in the control group (P<0.05).In sex stratification subgroup analysis, the frequencies of KLG-395A+F352V+C370C and KL A-395A+F352V+C370C were higherthan that in the controls of male subgroup (P<0.05). But the frequency of KLG-395A+F352V+C370S was lower than that in the controls of malesubgroup (P<0.05). The frequency of KL A-395A+F352V+C370S inpatients of female subgroup was obviously higher than that in the controls offemale subgroup (P<0.05).Conclusion:1. This study indicated that the patients who carried AA genotype of KLG-395A SNP and CC genotype of KL C-370S SNP have a higher risk tosuffer from CHD. The patients with CS genotype of KL C370S have a lowerrisk to suffer from CHD.2. This study indicated that the male patients who carried AA genotypeof KLG-395A SNP and CC genotype of KL C-370S SNP have a higher riskto suffer from CHD. The male patients with CS genotype of KL C370S have a lower risk to suffer from CHD.3. This study also found that the patients who carried KLG-395A+F352V+C370C, KLA-395A+F352V+C370C，KLA-395A+F352V+C370S have a higher riskto suffer from CHD. However, the patients with KLG-395A+F352V+C370S have a lower risk to suffer from CHD.4. This study also implied that the male patients who carried with KLG-395A+F352V+C370C and KL A-395A+F352V+C370C and the femalepatients who carried with KL A-395A+F352V+C370S have a higher risk tosuffer from CHD. However, the male patients carried KLG-395A+F352V+C370S have a lower risk to suffer from this disease.