Significant Association Between RGS14 Rs12654812 And Urolithiasis Risk Among Guangxi Population In China

[Objective]Nephrolithiasis is a worldwide health problem that affects almost all populations.This study aimed to evaluate the association between rs12654812 of Regulator of G-protein signaling 14?RGS14?gene and urolithiasis in the Chinese population.[Materials and methods]We collected questionnaires and blood samples from 830 patients with urolithiasis and 711 healthy controls in Guangxi Zhuang Autonomous Region,China.The age,sex,BMI,history of hypertension,history of diabetes,smoking status,drinking status,creatinine,uric acid,urea nitrogen were analyzed between the case group and control group.The polymorphism of RGS14 gene?rs12654812?was tested by the SNP scan^TM technology.In addition,eQTL analysis was conducted for RGS14 SNP.All statistical tests were carried out by the SPSS22.0 and plink1.07 software.Measurement data were analyzedusing t test,and count data were analyzed using chi-square test.The association between genetic loci and the risk factors of urolithiasis was assessed using Logistic regression models.[Results]BMI,hypertension,smoking status,drinking status,creatinine,uric acid were significantly differences in the urolithiasis patients compared with controls?P<0.05?.The distribution frequencies of the SNP genotype in the two groups followed the Hardy-Weinberg Equilibrium?P>0.05?.In cases,the frequencies of the G/G,G/A,and A/A alleles were 59.5%,35.1%and 5.4%,and the corresponding frequency were 63.2%,30.9%and 5.9%in the control group.There was no statistical difference in the frequency of genotype distribution among groups?P>0.05?.We found that the G/A+A/A genotypes?OR=1.361,95%CI=1.033-1.794,P=0.029?of rs12654812 had a significantly increased urolithiasis risk after adjusting for age,sex,BMI,smoking status,drinking status and history of hypertension,compared with G/G genotype.This hazardous effect was more pronounced in subgroup of age<50?OR=1.548,95%CI=1.075-2.228,P=0.019?,ever smoking?OR=1.929,95%CI=1.119-3.327,P=0.018?,ever drinking?OR=1.722,95%CI=1.146-2.588,P=0.009?,creatinine normal?OR=1.535,95%CI=1.130-2.084,P=0.006?and high uric acid?OR=1.869,95%CI=1.024-3.413,P=0.042?.The G/A genotype?OR=1.360,95%CI=1.019-1.816,P=0.037?of rs12654812 also had a significantly increased urolithiasis risk compared with G/G genotype.In case group,the frequency of G allele and A allele were 77.0%and 23.0%,and the frequency of G allele and A allele were 78.6%and 21.4%in control group.There was no significant differences between case and control group in the frequency distribution of per-allele?P>0.05?,but after adjusting for age,sex,BMI,smoking status,drinking status and history of hypertension,the A allele?OR=1.277,95%CI=1.013-1.609,P=0.038?of rs12654812 significantly increased the risk of urolithiasis compared with G allele.In addition,we performed an eQTL analysis of the rs12654812 and found that this polymorphism can affect multiple gene expression including RGS14 in multiple organs in humans.[Conclusions]We confirmed the association between the rs12654812polymorphism of the RGS14 gene and urolithiasis in Chinese population for the first time.This mutation may affect the adjacent SLC34A1 gene,which can affect the body's phosphorus metabolism,and ultimately lead to the formation of urolithiasis.Our results suggest that the rs12654812 polymorphism is one of the risk factors for urolithiasis,and it may become a genetic marker for susceptibility to urolithiasis in the future.