You have accessJournal of UrologyStone Disease: Basic Research (I)1 Apr 20132082 ASSOCIATION OF THE LOCI 5Q35.3, 7Q14.3, AND 13.Q14.1 WITH UROLITHIASIS: A CASE-CONTROL STUDY IN THE JAPANESE POPULATION, INVOLVING GENOME-WIDE ASSOCIATION STUDY Takahiro Yasui, Atsushi Okada, Masayuki Usami, Shuzo Hamamoto, Ryosuke Ando, Yasunori Itoh, Shoichi Sasaki, Keiichi Tozawa, Yoshihito Higashi, Yoshikazu Sato, and Kenjiro Kohri Takahiro YasuiTakahiro Yasui Nagoya, Japan More articles by this author , Atsushi OkadaAtsushi Okada Nagoya, Japan More articles by this author , Masayuki UsamiMasayuki Usami Nagoya, Japan More articles by this author , Shuzo HamamotoShuzo Hamamoto Nagoya, Japan More articles by this author , Ryosuke AndoRyosuke Ando Nagoya, Japan More articles by this author , Yasunori ItohYasunori Itoh Nagoya, Japan More articles by this author , Shoichi SasakiShoichi Sasaki Nagoya, Japan More articles by this author , Keiichi TozawaKeiichi Tozawa Nagoya, Japan More articles by this author , Yoshihito HigashiYoshihito Higashi Kyoto, Japan More articles by this author , Yoshikazu SatoYoshikazu Sato Sapporo, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2501AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To identify the genetic factors related with urolithiasis, we conducted a 3-stage genome-wide association study (GWAS) and case-control study to investigate the risk of urolithiasis by using single nucleotide polymorphism (SNP) analysis. METHODS A 3-stage GWAS was conducted using 5,892 urolithiasis cases and 17,809 controls, both of which were of Japanese origin. We investigated the association of novel loci with urolithiasis by using case-control association analysis for 601 cases and 201 control subjects from an independent Japanese sample set. Furthermore, the risk of urolithiasis was calculated from the total number of significant risk-allele associations by SNP analysis. RESULTS From the GWAS, 3 novel loci for urolithiasis were found: RGS14-SLC34A1-PFN3-F12 on 5q35.3, INMT-FAM188B-AQP1 on 7p14.3, and DGKH on 13q14.1. In a case-control association analysis, 7 SNPs were selected: 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). The SNPs rs12654812 at 5q35.3, rs12669187 at 7p14.3, and rs7981733 at 13p14.1 were significantly associated with urolithiasis, following a Bonferroni 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). In addition, meta-analysis of the current study and the GWAS exhibited significant associations, with p-values of 1.42 × 10-13, 1.25 × 10-15, and 5.81 × 10-10. We also found that these 3 SNPs have cumulative effects; individuals with 3 or more risk alleles had a 5.9-fold higher risk for urolithiasis than those with only 1 risk allele (Figure). CONCLUSIONS SLC34A1 in 5q35.1 and the AQP1 gene in 7p14.3 encode NPT2, a member of the type II sodium-phosphate co-transporter family, and aquaporin-1, a member of the major intrinsic protein family that regulates water flow, respectively. Both of these proteins are highly expressed in kidneys. Three novel susceptibility loci at 5q35.5, 7p14.33, and 13q14 were found to be associated with urolithiasis risk. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e854 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takahiro Yasui Nagoya, Japan More articles by this author Atsushi Okada Nagoya, Japan More articles by this author Masayuki Usami Nagoya, Japan More articles by this author Shuzo Hamamoto Nagoya, Japan More articles by this author Ryosuke Ando Nagoya, Japan More articles by this author Yasunori Itoh Nagoya, Japan More articles by this author Shoichi Sasaki Nagoya, Japan More articles by this author Keiichi Tozawa Nagoya, Japan More articles by this author Yoshihito Higashi Kyoto, Japan More articles by this author Yoshikazu Sato Sapporo, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...