Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.
J Urol. 2011 May;185(5):1742-6. doi: 10.1016/j.juro.2010.12.094. Epub 2011 Mar 21.
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.
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.
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.
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.
储存操作钙内流被认为是调节非兴奋细胞炎症反应的一个重要因素。然而，储存操作钙通道的主要组成部分 ORAI1 的遗传多态性对肾结石和结石复发的影响尚不清楚。我们研究了台湾患者肾结石与 ORAI1 基因遗传变异之间的关系。
对 136 例肾结石患者和 500 例对照进行病例对照研究。选择 5 个 ORAI1 的标签单核苷酸多态性进行基因分型。通过 TaqMan®assay 确定 ORAI1 基因型。评估病例和对照组的 Hardy-Weinberg 平衡，并通过卡方检验和滑动窗口单体型分析评估遗传效应。根据家族史进行亚组分析。
ORAI1 基因的两个单核苷酸多态性(rs12313273 和 rs6486795)与肾结石的风险相关。rs12313273 的 C 等位基因携带者与患者复发性结石形成密切相关。在滑动窗口分析中，rs12313273 和 rs7135617)和 3(rs12313273、rs7135617 和 rs6486795)单核苷酸多态性单体型的结果对肾结石的风险比单核苷酸多态性 rs12313273 具有更显著的影响。
据我们所知，这是首次发现 ORAI1 基因的新多态性可能导致钙肾结石和疾病复发的风险增加。
