KL基因单核苷酸多态性及其组合与老年高血压的相关性研究  

Association of single nucleotide polymorphisms and combination genotype distributions of the KL gene with essential hypertension in the aged

作　　者：刘晓林[1] 马厚勋[1] 田小春[1] 吴平[1] 周平[1] 吴蔚[2] 

机构地区：[1]重庆医科大学附属第一医院老年病科,重庆400016 [2]重庆医科大学附属第一医院耳鼻喉科,重庆400016

出　　处：《重庆医科大学学报》2011年第4期389-393,共5页Journal of Chongqing Medical University

基　　金：国家自然基金资助项目(编号:30672212);重庆医科大学创新基金资助项目(编号:CX0507)

摘　　要：目的:研究重庆地区老年汉族人群克老素(Klotho,KL)基因3个单核苷酸多态性及其组合分布规律,揭示其与老年高血压的相关性。方法:同期选择老年原发性高血压病人775例,正常健康老年人339例(年龄≥60岁)作为研究对象。提取外周血白细胞基因组DNA,应用单一等位基因特异性引物PCR技术(SASP-PCR)检测KL基因3个SNP位点的基因型,分析各等位基因及其组合与高血压病的相关性。结果:高血压病组KL基因G-395ASNP AA等位基因频率较对照组增高(P<0.01),若按性别分层研究,高血压组男性患者其AA等位基因型频率较对照组明显增高(P=0.001)。高血压病组KL基因C370S SNP及F352V SNP各等位基因型频率较对照组均无显著性差异(P>0.05)。组合分布研究发现:高血压病组KL G-395A+F352V+C370C、KL A-395A+F352V+C370C与KL A-395A+F352V+C370S组合基因型频率较对照组明显增高(P<0.05),按性别分层研究则发现仅在高血压病组男性患者其KL G-395A+F352V+C370C、KL A-395A+F352V+C370C及KL A-395A+F352V+C370S组合分布基因型频率较对照组增高有显著性差异(P<0.05)。本研究还发现在高血压病组男性患者其KLA-395A+F352F+S370S及KLG-395G+V352V+C370S组合分布基因型频率较对照组减低,且有显著性差异(P<0.040)。结论:本文研究发现在老年男性KL基因G-395A SNP与高血压病有明确相关性。组合分布研究还发现KLG-395A+F352V+C370C、KLA-395A+F352V+C370C及KL A-395A+F352V+C370S组合基因型与老年高血压病有关,并存在性别差异性,也就提示携带上述组合基因型的老年男性更易患高血压病。Objective ： To investigate the distribution of three cites of single nucleotide polymorphisms （ SNPs ） and their combination distributions of the KL gene in the Chinese elderly population and analyze their association with hypertension in the aged. Methods： Selected 775 patients with essential hypertension （ EH ） and 339 heathy people （ the age≥ 60 ） as research objects. Genomic DNA of leukocytes was extracted from venous blood and the 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 KL gene in order to analysis their relations with the EH. Results：The frequency of allele AA genotype of KL G-395A in EH group was higher than that in the control group （ P 〈 0.01 ）. According to sex strati- fication analysis, the frequency of allele AA 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 C370S SNP or F352V SNP between EH group and the control group （ P〉0.5 ）. 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 group was higher than that in the control group （P〈 0.05）,but according to sex stratification analysis,we only found that the allele genotype frequency of KL G-395A＋F352V＋ C370C,KL A-395A＋F352V＋C370C and KL A-395A＋F352V＋C370S were obviously higher in the EH male subgroup 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 ）. Conclusion：This study showed that there was an association between SNP of KL G-395A and essential hypertension in the aged.According to t

关 键 词：KLOTHO 高血压病 老年 组合基因型 

分 类 号：R544.1[医药卫生—心血管疾病]