TRPV5基因多态性与肾含钙结石疾病的相关性研究

Association Analysis between Kidney Stone Disease and Polymorphism of TRPV5 Gene

目的研究TRPV5基因多态性与含钙肾结石疾病的相关性研究,找出肾结石易感的单核苷酸多态性位点,进一步研究含钙肾结石分子发病机制。方法研究组随机选择2017年10月至2020年7月在厦门市第三医院确诊的肾含钙肾结石237例患者,对照组选择我院同期的无肾结石病史及影像学检查无肾结石的149名健康者,收集每位患者的一般资料及临床检验指标。选取与肾结石形成相关的基因TRPV5和UMOD,通过Hapmap数据库及haploview4.2软件筛选出2个基因的标签SNP的6位点,采用Illumina高通量二代测序方法进行基因分型技术,检测研究组及对照的相关基因的6个SNP位点;采用Logistic回归分析影响含钙肾结石发病的危险因素;并分析SNP基因型与肾结石易感性的关系。结果研究组的体质量指数(BMI)、血尿酸、血肌酐、收缩压及收缩压显著高于对照组(P<0.05),其他指标差异无统计学意义(P>0.05)。对TRPV5、UMOD基因6个多态性位点的基因型进行分析比较时,研究组TRPV5基因rs17212位点的等位基因A的频率显著高于对照组(P<0.05),rs17212位点AA、GA的基因型显著高于对照组(P<0.05),UMOD基因rs11648131位点的等位基因C的频率显著高于对照组(P<0.05),rs11648131位点CC的基因型显著高于对照组(P<0.05)。Logistic回归分析结果显示年龄≤35岁、BMI和rs17212是含钙肾结石的危险因素(P<0.05),rs11648131是含钙肾结石保护因素(P<0.05),但血尿酸与含钙肾结石的无明显相关性(P>0.05)。结论年龄≤35岁、BMI和rs17212与含钙肾结石的发生密切相关,rs11648131是含钙肾结石保护因素。

Objective To identify the susceptibility factors and susceptibility gene sites of case-urinary calculi,and to further confirm the molecular pathogenesis of urolithiasis.Methods The research group randomly selected 237 patients with calcium-containing nephrolithiasis diagnosed in Xiamen Third Hospital from October 2017 to July 2020,and the control group selected 149 patients with no history of nephrolithiasis and no nephrolithiasis by imaging examination in our hospital during the same period.The general information and clinical test indexes of each patient were collected.The genes TRPV5 and UMOD related to the formation of kidney stones were selected,and the 6 loci of the tag SNPs of the two genes were screened by Hapmap database and haploview4.2 software,and the Illumina high-throughput next-generation sequencing method was used for genotyping technology.6 SNP loci of related genes in the control group and control group;Logistic regression was used to analyze the risk factors for the incidence of calciumcontaining kidney stones;and the relationship between SNP genotype and susceptibility to kidney stones was analyzed.Results The body mass index(BMI),serum uric acid,serum creatinine,systolic blood pressure and systolic blood pressure of the study group were significantly higher than those of the control group(P<0.05),and other indicators had no significant difference(P>0.05).When we compared the genotypes of the three polymorphic sites of the TRPV5 gene,we found that only the rs17212 polymorphism was significantly associated with the risk of urolithiasis.Compared with the GA homozygous genotype carrier,the genotype of AA at rs11648131 locus was significantly higher than the control group(P<0.05).And the rs11648131 polymorphism in the three polymorphic loci of the UMOD gene was significantly associated with the protection of urolithiasis.The genotype of CC at rs11648131 locus was significantly higher than that of the control group(P<0.05).Logistic regression analysis showed that age less than 35 years old,BMI and rs17212 were risk factors for calcium-containing kidney stones(P<0.05),and rs11648131 was a protective factor for calcium-containing kidney stones(P<0.05).but blood uric acid is related to calcium-containing kidney stones.There was no significant correlation with calcium kidney stones(P>0.05).Conclusion Age less than 35 years,BMI,and rs17212 are closely related to the occurrence of calcium-containing kidney stones,and rs11648131 is a protective factor for calcium-containing kidney stones.