Heparan Sulfate Proteoglycan Gene Polymorphism And Genetic Susceptibility To Calcium Oxalate Nephrolithiasis

Objective:1.To explore the potential association between the Heparan Sulfate Proteoglycan gene polymorphism and genetic susceptibility to calcium oxalate nephrolithiasis in Chinese Han population.2.To investigate correlation of the Heparan Sulfate Proteoglycan gene polymorphism with calcium oxalate stone recurrence.Methods:In this study,totally 143 patients diagnosed with calcium oxalate urolithiasis were studied.In addition,157 age-matched healthy controls were enrolled.Genomic DNA were extracted from blood samples.Based on case-control study,Heparan Sulfate Proteogylcan gene polymorphism (rs3767140) was determined by polymerase chain reaction and restriction fraction length polymorphism(PCR-RFLP) with BamH I digestion.The correlation of the heparan sulfate proteoglycan gene polymorphism with calcium oxalate stone and calcium oxalate stone recurrence was investigated.Meanwhile age,sex composition,weight,height and body mass index (BMI) were analyzed.All statistical tests were carried out by the SPSS 13.0 software.The associations of clinical features,including age,weight,hight and body mass index (BMI), were tested using T test.Measurement date interclass was indicated with x±s.The differences in sex composition and genotype frequencies between the cases and controls were tested using x2-test. Unconditional logistic regression model was used to assess the association between correlative factors and calcium oxalate stone recurrence.Results:Differences of age,sex composition,weight,height and body mass index (BMI) between the two groups were not significant(P>0.05).The distribution frequencies of site rs3767140 genotype and alleles in the two groups followed the Hardy-Weinberg equilibrium(P> 0.05).The distribution frequencies of the GG+GT,TT genotypes were 69.23%,30.77% in oxalate calcium urolithiasis group and 79.62%,20.38% respectively in healthy control group.The differences between the two groups were statistically significant(P<0.05).The distribution frequencies of G and T alleles in stone and control groups were 45.10%,55.90% and 54.14%,45.86% respectively,and statistical differences were observed(P<0.05).The subjects with TT genotype yielded a 1.736 fold increased risk for calcium oxalate nephrolithiasis,compared with subjects with GT+GG genotype(OR=1.736,95%CI=1.026～2.938),however,we did not find the association between HSPG gene polymorphism and the possibility of stone recurrence.Conclusions:1.There are G/T polymorphisms in HSPG gene in Chinese Han population of Shandong Province.The allele G frequency in healthy control is about 54.14%.2.There is significant association between HSPG gene polymorphism and calcium oxalate nephrolithiasis. The TT genotype may be a good genetic marker for calcium oxalate nephrolithiasis.The subjects with TT genotype yielded a 1.736 fold increased risk for calcium oxalate nephrolithiasis,compared with subjects with GT+GG genotypes.3.Allele G may be a protective factor for calcium oxalate nephrolithiasis..4.There is no significant association between HSPG gene polymorphism and calcium oxalate stone recurrence.