title: A polymorphism of the ORAI1 gene is associated with the risk and recurrence of calcium nephrolithiasis.
abstract: OBJECTIVE
  Store-operated calcium entry has been considered an important factor to regulate inflammatory reactions in nonexcitable cells. However, the effects of genetic polymorphisms of ORAI1, a main component of store-operated calcium channels, on nephrolithiasis and stone recurrence remain unclear. We investigated the association between calcium containing nephrolithiasis and genetic variants of ORAI1 gene in Taiwanese patients.
  
  
  METHODS
  A case-control study was performed in 136 patients with nephrolithiasis and 500 controls. Five tagging single nucleotide polymorphisms of ORAI1 were selected for genotyping. ORAI1 genotypes were determined by TaqMan® assay. Hardy-Weinberg equilibrium in cases and controls was assessed, and genetic effects were evaluated by the chi-square test and sliding window haplotype analysis. Subset analysis was done according to family history.
  
  
  RESULTS
  Two single nucleotide polymorphisms (rs12313273 and rs6486795) of the ORAI1 gene were associated with the risk of nephrolithiasis. The C allele carrier for rs12313273 was strongly related to recurrent stone forming in patients. On sliding window analysis the results of the 2 (rs12313273 and rs7135617) and the 3 (rs12313273, rs7135617 and rs6486795) single nucleotide polymorphism haplotypes had more significant effects on the risk of nephrolithiasis than the single nucleotide polymorphism rs12313273.
  
  
  CONCLUSIONS
  To our knowledge this is the first study identifying the novel polymorphisms of the ORAI1 gene, which may predispose to the risk of calcium nephrolithiasis and disease recurrence.
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.
authors.forename: Yii-Her
authors.initials: YH
authors.lastname: Chou
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chiu
authors.forename: Mu-En
authors.initials: ME
authors.lastname: Liu
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chen
authors.forename: Chen-Chia
authors.initials: CC
authors.lastname: Chang
authors.forename: Wei-Pin
authors.initials: WP
authors.lastname: Chang
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics*; D020013:Calcium Signaling / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000235:genetics*; D000071740:ORAI1 Protein; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012306:Risk; D013624:Taiwan
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D002118:Calcium