title: Association between polymorphisms in osteopontin gene (SPP1) and first episode calcium oxalate urolithiasis.
abstract: 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.
authors.affiliation: Clinical Center for Urological Disease Diagnosis and Private Clinic Specialized in Urological and Andrological Genetics, P.O. Box 19395-1849, Tehran, Iran. info@safarinejad.com
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Safarinejad
authors.forename: Nayyer
authors.initials: N
authors.lastname: Shafiei
authors.forename: Shiva
authors.initials: S
authors.lastname: Safarinejad
mesh_terms: D000328:Adult; D002118:Calcium / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000097:blood / Q000235:genetics* / Q000652:urine; D053495:Osteopontin / Q000097:blood / Q000235:genetics* / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C506895:SPP1 protein, human; D053495:Osteopontin; D002118:Calcium