A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1.
A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1.
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DOI：
10.1371/journal.pgen.1002541
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Matsuda K
中科院分区：
文献类型：
--
作者：
Urabe Y;Tanikawa C;Takahashi A;Okada Y;Morizono T;Tsunoda T;Kamatani N;Kohri K;Chayama K;Kubo M;Nakamura Y;Matsuda K
肾结石是一种常见的肾脏疾病，病因复杂。为了确定肾结石的遗传因素，我们进行了一项三阶段全基因组关联研究（GWAS），共使用了5，892例日本肾结石病例和17，809例日本对照。在这里，我们发现了三个新的肾结石基因座：5q35.3上的RGS 14-SLC 34 A1-PFN 3-F12（rs 11746443; P = 8.51×10−12，比值比（OR）= 1.19），7p14.3上的INMT-FAM 188 B-AQP 1（rs 1000597; P = 2.16×10−14，OR = 1.22）和13q14.1上的DGKH（rs 4142110; P = 4.62×10−9，OR = 1.14）。 随后对21，842名日本受试者的分析显示，SNP rs 11746443与估计肾小球滤过率（eGFR）降低相关（P = 6.54×10−8），表明这种变化在肾功能中起着至关重要的作用。 我们的研究结果阐明了遗传变异在肾结石发病机制中的重要性。虽然肾结石是最常见的肾泌尿系统疾病之一，具有高患病率（4%-9%）和极高的复发率（10年内60%），但对其发病机制中常见变异的作用知之甚少。通过GWAS共使用5，892例病例和17，809例对照，我们确定了三个新的肾结石位点：rs 11746443，rs 1000597和rs 4142110（P<1×10−8）。最重要的两个SNPs rs 11746443和rs 1000597分别位于SLC 34 A1和AQP 1基因的上游，这两个基因分别在肾功能和尿液浓缩过程中发挥重要作用。我们还发现SNP rs 11746443与估计肾小球滤过率（eGFR）的降低相关，表明这种变化在肾功能中的作用。虽然肾结石被认为是与生活方式有关的疾病之一，但饮食干预研究以降低复发率的结果并不成功。我们的研究结果有助于更好地了解肾结石的发病机制，并导致新的治疗方法的发展。
Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P = 8.51×10−12, odds ratio (OR) = 1.19), INMT-FAM188B-AQP1 on 7p14.3 (rs1000597; P = 2.16×10−14, OR = 1.22), and DGKH on 13q14.1 (rs4142110; P = 4.62×10−9, OR = 1.14). Subsequent analyses in 21,842 Japanese subjects revealed the association of SNP rs11746443 with the reduction of estimated glomerular filtration rate (eGFR) (P = 6.54×10−8), suggesting a crucial role for this variation in renal function. Our findings elucidated the significance of genetic variations for the pathogenesis of nephrolithiasis. Although nephrolithiasis is one of the most common nephro-urological disorders with high prevalence (4%–9%) and extremely high recurrence rate (60% within ten years), little is known about the role of common variations in its pathogenesis. Through a GWAS using a total of 5,892 cases and 17,809 controls, we identified three novel nephrolithiasis loci: rs11746443, rs1000597, and rs4142110 (P<1×10−8). The top two significant SNPs, rs11746443 and rs1000597, are located upstream of the SLC34A1 and the AQP1 genes that play important roles in kidney function and the urine-concentration process, respectively. We also found that SNP rs11746443 is associated with the reduction of estimated glomerular filtration rate (eGFR), indicating the role of this variation in kidney function. Although nephrolithiasis is considered as one of the lifestyle-related diseases, the results of dietary intervention studies to reduce the recurrence incidence have been unsuccessful. Our findings could contribute to a better understanding of the pathogenesis of nephrolithiasis and lead to the development of new therapeutics.
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影响因子：
4.5
作者：
Okada Y;Hirota T;Kamatani Y;Takahashi A;Ohmiya H;Kumasaka N;Higasa K;Yamaguchi-Kabata Y;Hosono N;Nalls MA;Chen MH;van Rooij FJ;Smith AV;Tanaka T;Couper DJ;Zakai NA;Ferrucci L;Longo DL;Hernandez DG;Witteman JC;Harris TB;O'Donnell CJ;Ganesh SK;Matsuda K;Tsunoda T;Tanaka T;Kubo M;Nakamura Y;Tamari M;Yamamoto K;Kamatani N
通讯作者：
Kamatani N
影响因子：
3.3
作者：
Barnett, J. H.;Smoller, J. W.
通讯作者：
Smoller, J. W.
DOI：
10.1073/pnas.95.9.5372
发表时间：
1998-04-28
影响因子：
11.1
作者：
Beck, L;Karaplis, AC;Tenenhouse, HS
通讯作者：
Tenenhouse, HS
影响因子：
13.2
作者：
Matsuo, Seiichi;Imai, Enyu;Hishida, Akira
通讯作者：
Hishida, Akira
影响因子：
48
作者：
De Jager, Philip L.;Chibnik, Lori B.;Cui, Jing;Reischl, Joachim;Lehr, Stephan;Simon, K. Claire;Aubin, Cristin;Bauer, David;Heubach, Juergen F.;Sandbrink, Rupert;Tyblova, Michaela;Lelkova, Petra;Havrdova, Eva;Pohl, Christoph;Horakova, Dana;Ascherio, Alberto;Hafler, David A.;Karlson, Elizabeth W.
通讯作者：
Karlson, Elizabeth W.