Gao B, Yasui T, Itoh Y, Li Z, Okada A, Tozawa K, Hayashi Y, Kohri K
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
Kidney Int. 2007 Sep;72(5):592-8. doi: 10.1038/sj.ki.5002345. Epub 2007 May 23.
Osteopontin (OPN) is one of the glycosylated phosphoproteins produced in the kidney that can modulate nephrolithiasis. We had previously found a modest association between OPN gene polymorphisms and the risk for urinary stone formation. In order to determine if sequence variants within the OPN gene could be linked to the risk of nephrolithiasis; we sequenced the entire OPN gene of 45 stone forming patients and 54 control patients of Japanese ancestry. We identified 61 polymorphisms and of these evaluated four haplotype-tagging single nucleotide polymorphisms in a total of 126 kidney stone cases and 214 healthy individuals; all of Japanese ancestry. There was a significant association of two of these haplotypes located in the OPN promoter with the relative probability of nephrolithiasis; one of increased and one of reduced risk. Our findings provide potential support for significant increased and decreased associations between OPN gene haplotypes and the relative potential of stone formation in the Japanese population. We suggest that such genetic findings may help to clarify the function of OPN in nephrolithiasis.
骨桥蛋白（OPN）是肾脏产生的糖基化磷蛋白之一，可调节肾结石形成。我们之前发现OPN基因多态性与尿石形成风险之间存在适度关联。为了确定OPN基因内的序列变异是否与肾结石风险相关；我们对45名结石形成患者和54名日本血统对照患者的整个OPN基因进行了测序。我们鉴定出61种多态性，并在总共126例肾结石病例和214名健康个体（均为日本血统）中评估了4个单倍型标签单核苷酸多态性。位于OPN启动子中的其中两个单倍型与肾结石的相对概率存在显著关联；一个增加风险，一个降低风险。我们的研究结果为OPN基因单倍型与日本人群结石形成相对可能性之间显著增加和降低的关联提供了潜在支持。我们认为，此类遗传学发现可能有助于阐明OPN在肾结石形成中的作用。
