Clinical Center for Urological Disease Diagnosis and Private Clinic Specialized in Urological and Andrological Genetics, P.O. Box 19395-1849, Tehran, Iran.
Urolithiasis. 2013 Aug;41(4):303-13. doi: 10.1007/s00240-013-0582-7. Epub 2013 Jun 20.
We examined whether single nucleotide polymorphisms (SNPs) in SPP1 gene are associated with risk of calcium oxalate urolithiasis (COU). We genotyped nine known SNPs in SPP1 gene (rs11739060, rs28357094, rs2728127, rs11730582, rs1126772, rs9138, rs2853744, rs4754=p.Asp80Asp, and rs1126616=p.Ala236Ala). Genomic DNA from 1,026 individuals (n = 342 patients with first episode COU, and n = 684 healthy unrelated controls) was analyzed for nine SPP1 SNPs using polymerase chain reaction and melting curve analysis by means of a pair of fluorescence resonance energy transfer probes. Serum and urine osteopontin (OPN) levels were also measured using enzyme-linked immunosorbent assay kits. rs9138 AA genotype was protective (OR 0.62, 95 % CI 0.47-0.81; P = 0.004). rs28357094 TT genotype (OR 2.52, 95 % CI 1.74-3.79; P = 0.021), rs2728127 GG genotype (OR 2.64, 95 % CI 1.42-4.81; P = 0.002), and rs2853744 GG genotype (OR 1.68, 95 % CI 1.22-3.87; P = 0.003) were predisposing. None of the other examined SPP1 SNPs was associated with COU susceptibility. Subjects with protective and predisposing polymorphisms had increased and decreased serum levels of OPN, respectively. Urinary calcium/OPN ratios were higher and lower in subjects with predisposing and protective SNPs of SPP1 gene, respectively. Of 28 constructed haplotypes, 6 demonstrated significant association with COU risk. There was no sex difference in the obtained results. The SPP1 gene polymorphisms are associated with the COU susceptibility.
我们研究了 SPP1 基因中的单核苷酸多态性（SNPs）是否与草酸钙尿石症（COU）的风险相关。我们对 SPP1 基因中的九个已知 SNPs（rs11739060、rs28357094、rs2728127、rs11730582、rs1126772、rs9138、rs2853744、rs4754=Asp80Asp 和 rs1126616=Ala236Ala）进行了基因分型。使用聚合酶链反应和熔解曲线分析，通过一对荧光共振能量转移探针，对 1026 名个体（n=342 名首次发作 COU 的患者和 n=684 名健康无关对照）的 9 个 SPP1 SNPs 进行了分析。还使用酶联免疫吸附试剂盒测量了血清和尿液骨桥蛋白（OPN）水平。rs9138 AA 基因型具有保护作用（OR 0.62，95%CI 0.47-0.81；P=0.004）。rs28357094 TT 基因型（OR 2.52，95%CI 1.74-3.79；P=0.021）、rs2728127 GG 基因型（OR 2.64，95%CI 1.42-4.81；P=0.002）和 rs2853744 GG 基因型（OR 1.68，95%CI 1.22-3.87；P=0.003）具有易感性。未发现其他研究的 SPP1 SNPs 与 COU 易感性相关。具有保护和易感性多态性的受试者的 OPN 血清水平分别升高和降低。SPP1 基因具有易感性和保护性多态性的受试者的尿钙/OPN 比值分别升高和降低。在构建的 28 个单倍型中，有 6 个与 COU 风险显著相关。结果没有性别差异。SPP1 基因多态性与 COU 易感性相关。
