Association Between Vitamin D Receptor Gene Polymorphism And Idiopathic Hypocitraturia In The Yunnan Yi Population And Detection Of VDR Gene Methylation

Objective(s):To investigate the association between rs2228570,rs7975232,rs731236,rs 1544410,rs10783218 and rs3847987 of vitamin D receptor gene polymorphism and idiopathic hypocitraturia in the Yunnan yi nationality and its clinical significance.Detection of methylation level of VDR gene.Methods:302 cases of idiopathic hypocitraturia and 258 controls with normal urinary citrate were selected from the Yunnan yi nationality,and the association between rs2228570,rs7975232,rs731236,rsl544410,rsl0783218 and rs3847987 of vitamin D receptor gene polymorphism with idiopathic hypocitraturia in the Yunnan nationality was analyzed by SNapShot detection.Five samples of Yunnan yi nationality were collected to extract gene DNA from blood(2 control cases and 3 idiopathic hypocitraturia cases)for the detection and analysis of Sequenom MassARRAY in three fragments of VDR gene.Results:There were significant diferences in the practical fequency and expected fequency between the six SNP sites in the hard-weinberg equilibrium(P>0.05).The mean urinary citrate content of 501 cases was(243.26±38.63)mg/24h and that of 378 controls was(591.58±125.89)mg/24h with the differences being statistically significant(P<0.05).There was significant difference in the genotype frequency difference of the VDR gene SNP rs7975232,rs731236,rs2228570,(P<0.05)between cases and controls.AA genotype of rs7975232,CC genotype of rs731236 and TT genotype of rs2228570 were more common in the group of patients with idiopathic low citrate than in the control group.In the 24h urine citric acid content of subjects in the two groups,AA genotype of rs7975232 was(365.71 195.23)mg/24h,significantly lower than CC and CA genotypes of rs7975232[(507.67 197.42),(485.55 180.15)mg/24h,P<0.05].The CC genotype of rs731236 was(366.92 186.43)mg/24h,significantly lower than that of the CC and CT genotypes of rs731236[(505.47196.02),(488.95 191.95)mg/24h,P<0.05].TT genotype of rs2228570 was(363.92185.43)mg/24h,significantly lower than that of CC and CT genotypes of rs2228570[(506.47 198.02),(485.95 190.95)mg/24h,P<0.05].Sample no.20(control)and no.109(case)of the first VDR gene segment(VDR I)were completely non-methylated.Sample no.22(control),124(case)and 158(case)showed incomplete methylation,in which case no.158 showed obvious methylation in the detection section.The second VDR gene segment(VDR Ⅱ)and the third VDR gene segment(VDR Ⅲ)were completely non-methylated,with no difference inmethylation degree between samples.Conclusion(s):There is a genetic correlation between idiopathic hypocitraturia of Yunnan yi nationality and SNP sites rs7975232,rs731236 and rs2228570 of VDR gene.AA genotype of rs7975232,CC genotype of rs731236 and TT genotype of rs2228570 are expected to be candidate genes for idiopathic hypocitraturia of Yunnan yi nationality.The methylation degree of VDR gene was different among the 5 samples,and the methylation degree of sample no.158(case)was higher than that of other samples.The methylation difference area was in the first section of the test,providing a direction for the later study of VDR gene methylation in stone patients.