Association Of Single Nucleotide Polymorphisms And Combination Genotype Distributions Of KLOTHO Gene With Essential Hypertension In The Aged

Objective To investigate the distribution of three sites of single nucleotide polymorphisms (SNPs)and their combination distributions of the Klotho gene in Chongqing Han nationality population in China in order to analyze association of SNPs of the Klotho gene with essential hypertension and left ventricle hypertrophy in the aged.Methods 775 patients with essential hypertension (EH) selected as EH group and 339 healthy people as control group. At the same time,361 patients selected from EH group who received the echocardiogram examinations were divided into two groups according to the diagnostic standards of left ventricular hypertrophy(LVH),such as 220 patients with left ventricular hypertrophy as LVH subgroup,141 patients without LVH as control subgroup. Genomic DNA of leukocytes was extracted from venous blood and single allele specific primer PCR technique (SASP-PCR) was used to detect allelic genotypes of three sites of SNPs and their distribution of combination genotypes of the Klotho gene. The ventricular inter-septum and posterior wall thickness were measured by echocardiograph examination in order to appraisal the extent of the LVH and their relationships of single nucleotide polymorphisms ( SNPs ) site and combination distributions of the Klotho gene with essential hypertension and left ventricular hypertrophy in the aged were analyzed.Results The frequency of allele AA genotype of KL G-395A in the EH male subgroup was obviously higher than that in the control subgroup(P=0.001). There were no significant difference to be found either in the KL F352V SNP or C370S SNP between EH group and the control group (P>0.05).But according to the combination genotype analysis, we found that the allelic genotype frequency of Klotho G-395A+F352V+C370C,Klotho A-395A+F352V+C370C and Klotho A-395A+F352V+C370S in the EH male subgroup were obviously higher than that in the healthy male subgroup (P<0.05). We also found that the combined allelic genotype frequency of KL A-395A+F352F+S370S and KL G-395G+V352V+C370S were obviously lower in the EH male subgroup than that in the control male subgroup (P<0.04).The frequency of allele AA genetype of G-395A SNP in the HP with LVH subgroup was higher than that in the control subgroup without LVH(P=0.041),but no gender difference was found according to sex stratification analysis(P>0.05).The frequency of allele GG genetype of Klotho G-395A in hypertension with LVH group was lower than that in the groups without LVH(P=0.044).According to sex stratification analysis, the frequency of allele GG was obviously lower in female patients in hypertension with LVH subgroup than that in the control subgroup without LVH (P=0.005).There were no significant difference to be found either in the KL F352V SNP or C370S SNP between the hypertension with LVH subgroup and the control subgroup without LVH (P>0.05).Conclusions This study showed that there was an association between KL G-395A SNP and essential hypertension in the aged,but there was not any relation to be found between SNPs of KL F352V and KL C370S and EH in the aged. According to the combination genotype analysis, this study found that combination genotypes of KL G-395A+F352V+C370C,KLA-395A+F352V+C370C and KL A-395A+ F352V+C370S were associated with EH in the aged and the sex difference to be found, i.e.the male individuals who carried with genotypes of KLG-395A+F352V+C370C,KLA-395A+F352V+C370C and KLA-395A+ F352V +C370S have a high risk in suffering from EH in the aged.This study found that the G-395A SNP of Klotho gene was related to EH with LVH in the aged, that is to say, the individuals carrying with AA allelotype of G-395A SNP were more easily suffering from LVH in the EH group. There was no association to be found between SNPs of KL F352V and KL C370S and LVH in the aged with essential hypertension.