| Objective: To explore the association between the CaSR gene polymorphisms and calcium nephrolithiasis in Gannan area in Jiangxi province.Methods: In all,220 cases of patients with calcium nephrolithiasis(CN group)and 250 cases of normal people(control group)in Gannan area in Jiangxi province were recruited in this study.The whole blood genome DNA in both groups was extracted with Axy Prep DNA extraction kit.Rs6776158,rs1501899 and rs7652589 single nucleotide polymorphisms(SNP)in CaSR gene were all detected by real-time fluorescent quantitative polymerase chain reaction Taq Man-MGB 5'-nuclease assay.And serum calcium,serum phosphorus,serum magnesium,uric acid,uric calcium,and urine p H in both groups were detected.Biochemical variables and the distribution of allele,haplotypes,genotype were compared between calcium nephrolithiasis patients and controls.Results: The calcium nephrolithiasis patients had higher uric concentrations of ionized calcium(10.589 ± 2.219 mg/d L)than control group(7.514 ± 1.715 mg/d L)(P<0.05).Using a logistic regression model,the increase in stone risk in participants was predicted by the higher of serum ionized calcium values(P<0.05).The genotype distribution of the individuals studied was in accordance to a population at Hardy Weinberg equilibrium(P>0.05).The distribution frequencies of the A and G alleles of rs1501899 in CN group and control group were 43.9%,56.1% and 60.8%,39.2%,respectively(P<0.05).The frequency of the AA,AG and GG genotype were 22.3%,43.2% and 34.5% in CN group,and 36.8%,48.0% and 15.2% in control group.The risk for CN of AA and AG genotype were 0.266 and 0.396 times that of GG genotype(P<0.05,OR=0.266,95% CI=0.158~0.449 and P<0.05,OR=0.396,95% CI=0.247~0.635,respectively).The allele and genotypes frequency at rs7652589 and rs6776158 SNPs was similar in calcium nephrolithiasis patients and controls(P>0.05).About 193 patients with AG or GG genotype at rs6776158 had a lower serum phosphorus than 27 patients carrying the AA genotype((1.080±0.232)mg/d L vs(1.189±0.161)mg/d L,respectively,P=0.019).And 356 of all participants with AA or AG genotype at rs1501899 had a lower urinary calcium concentrations than 114 of all participants carrying the GG genotype((8.776±2.471)mg/d L vs(9.509±2.493)mg/d L,respectively,P=0.006).There was no statistically significant difference in the relations between the genotypes for rs6776158 and rs7652589,and clinical phenotype(P>0.05).CaSR gene haplotype analysis showed that haplotype A-A-G ? G-G-A was positively correlated with the formation of calcium nephrolithiasis(OR=96.380,95% CI=23.726~391.512;OR=258.665,95% CI=63.868~1047.596),but haplotype A-G-G?G-A-A were negatively correlated with the formation of calcium nephrolithiasis(OR=0.099,95% CI=0.063~0.153;OR=0.114,95% CI=0.082~0.156).Conclusions: 1.CaSR gene polymorphisms were significantly associated with the formation of calcium nephrolithiasis in Gannan area in Jiangxi province.Genotype AA and AG in rs1501899,and haplotype A-G-G,G-A-A maybe decrease the risk of calcium nephrolithiasis formation,but genotype GG in rs1501899 and haplotype A-A-G,G-G-A maybe increase the risk of calcium nephrolithiasis formation.2.High urine calcium concentration maybe increase the risk of calcium nephrolithiasis formation. |
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