Studies On The Correlation Of Urolithiasis With Adhesion-related Genes And Their Variations

ObjectiveAdhesion of crystals with cells are the key factors affecting the formation of urolithiasis.The relationship between the polymorphism of the genes associated with adhesion and urolithiasis is not clear.This project is to investigate the correlation between the adhesion-related genes and the risk of urolithiasis.Methods242 patients with renal calculi(stone group)and 273 healthy subjects(control group)are collected.The genomic DNA is extracted from peripheral blood of all the subjects,and the components of the stones are analyzed by FTIR.Eight adhesion-related gene polymorphisms including CDH2(rs17445840),IL6(rs13306435),FAT4(rs12508222),ABL2(rs55655202),CX3CR1(rs3732379),ITGAE(rs2976230),FLOT2(rs3736238)and FAT1(rs11939575)obtained from previous exome sequencing studies are stereotyped by high-resolution melting analysis technique.Polymerase chain reaction is used to amplify the gene sequence,which is verified by the Sanger sequencing.The frequency of genotypes and alleles is calculated,and the chi-square test or Fisher's exact probability is used for statistical analysis.Haploview4.1 is used to analyze the linkage disequilibrium.ResultsAt rs17445840 of CDH2 gene,the frequency of CT genotype in calculi group is higher than that in control group(? 2 = 5.606,P = 0.018).Individuals with the CT genotype are 2.1 times more likely to form urolithiasis than those with the CC+TT genotype(OR = 2.103).Carriers of the T allele are 1.9 times more likely to form urolithiasis than individuals with the C allele(OR = 1.944).At rs13306435 of the IL6 gene in the age group under 40 years old,frequency of TA genotype in calculi group is higher than that of control group(P = 0.04).Individuals with the TA genotype are 11.7 times more likely to form urolithiasis than those with the TT genotype(OR = 11.727).Individuals with the A allele are 10.4 times more likely to form urolithiasis than those with the T allele(OR = 10.44).For rs12508222 with FAT4 gene,the risk of calcium oxalate stone in patients with G allele is 3.2 times higher than that in patients with an allele(OR = 3.184).There are no significant differences in genotype frequency and allele frequency of ABL2(rs55655202),CX3CR1(rs3732379),ITGAE(rs2976230),FLOT2(rs3736238)and FAT1(rs11939575).ConclusionsIndividuals with CT genotype and T allele at rs17445840 of CDH2 gene increase the risk of urolithiasis.TA genotype and A allele at the rs13306435 of IL6 gene in individuals under 40 years old increase the risk of urolithiasis.Patients with G allele of rs12508222 of FAT4 gene increase the risk of forming calcium oxalate stone.CDH2 gene rs17445840,IL6 gene rs13306435 and FAT4 rs12508222 are associated with the risk of urolithiasis.