A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population
A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population
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日本人群中 5q35.3、7p14.3 和 13q14.1 三个肾结石位点的重复研究
DOI：
10.1038/jhg.2013.59
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发表时间：
2013
期刊：
影响因子：
3.5
通讯作者：
Kohri K
中科院分区：
文献类型：
--
作者：
Yasui T;Okada A;Urabe Y;Usami M;Mizuno K;Kubota Y;Tozawa K;Sasaki S;Higashi Y;Sato Y;Kubo M;Nakamura Y;Matsuda K;Kohri K
先前的全基因组关联研究（GWAS）报告了5 q35处的三个新的肾结石易感基因座。3，7p14. 3和13 q14。1.在这里，我们调查了这些位点与肾结石的关联，通过使用一个独立的日本样本集。我们对601名肾结石患者和201名对照者进行了病例对照关联分析。我们选择了7个单核苷酸多态性（SNPs）：5 q35的rs 12654812和rs 11746443。3（RGS 14-SLC 34 A1-PFN 3-F12）;来自7 p14的rs 12669187和rs 1000597。3（INMT-FAM 188 B-AQP 1）;和来自13 q14的rs7981733、rs 1170155和rs 4142110。1（DGKH（二酰基甘油激酶）），这是以前报道的显着相关的肾结石。rs 12654812、rs 12669187和rs7981733与Bonferroni校正后的肾结石显著相关（分别为P= 3.12× 10− 3，OR = 1.43; P= 6.40× 10− 3，OR= 1.57; P= 5.00× 10− 3，OR= 1.41）。当前和既往GWAS结果的荟萃分析表明，与肾结石显著相关（P值分别为7.65× 10− 15、7.86× 10− 14和1.06× 10− 9）。我们观察到这三个SNP的累积效应;具有三个或更多风险等位基因的个体患肾结石的风险是仅具有一个风险等位基因的个体的5.9倍。我们的研究结果阐明了日本人群肾结石中这三个位点的遗传变异的意义。
A previous genome-wide association study (GWAS) reported three novel nephrolithiasis-susceptibility loci at 5q35. 3, 7p14. 3 and 13q14. 1. Here, we investigated the association of these loci with nephrolithiasis by using an independent Japanese sample set. We performed case–control association analysis using 601 patients with nephrolithiasis and 201 control subjects. We selected seven single-nucleotide polymorphisms (SNPs): rs12654812 and rs11746443 from 5q35. 3 (RGS14-SLC34A1-PFN3-F12); rs12669187 and rs1000597 from 7p14. 3 (INMT-FAM188B-AQP1); and rs7981733, rs1170155, and rs4142110 from 13q14. 1 (DGKH (diacylglycerol kinase)), which were previously reported to be significantly associated with nephrolithiasis. rs12654812, rs12669187 and rs7981733 were significantly associated with nephrolithiasis after Bonferroni’s correction (P= 3.12× 10− 3, odds ratio (OR)= 1.43; P= 6.40× 10− 3, OR= 1.57; and P= 5.00× 10− 3, OR= 1.41, respectively). Meta-analysis of current and previous GWAS results indicated a significant association with nephrolithiasis (P= 7.65× 10− 15, 7.86× 10− 14 and 1.06× 10− 9, respectively). We observed a cumulative effect with these three SNPs; individuals with three or more risk alleles had a 5.9-fold higher risk for nephrolithiasis development than those with only one risk allele. Our findings elucidated the significance of genetic variation at these three loci in nephrolithiasis in the Japanese population.