title: Association between single-nucleotide polymorphisms in selectin genes and immunoglobulin A nephropathy.
abstract: Although intensive efforts have been undertaken to elucidate the genetic background of immunoglobulin A nephropathy (IgAN), genetic factors associated with the pathogenesis of this disease are still not well understood. We designed a case-control association study that was based on linkage disequilibrium among single-nucleotide polymorphisms (SNPs) in the selectin gene cluster on chromosome 1q24-25, and we found two SNPs in the E-selectin gene (SELE8 and SELE13) and six SNPs in the L-selectin gene (SELL1, SELL4, SELL5, SELL6, SELL10, and SELL11) that were significantly associated with IgAN in Japanese patients. All eight SNPs were in almost complete linkage disequilibrium. SELE8 and SELL10 caused amino acid substitutions from His to Tyr and from Pro to Ser (chi2=9.02, P=.0026, odds ratio = 2.73 [95% confidence interval [CI] 1.38--5.38] for His-to-Tyr substitutions; chi2=17.4, P=.000031, odds ratio = 3.61 [95% CI 1.91--6.83] for Pro-to-Ser substitutions), and SELL1 could affect promoter activity of the L-selectin gene (chi2=19.5, P=.000010, odds ratio = 3.77 [95% CI 2.02--7.05]). The TGT haplotype at these three loci was associated significantly with IgAN (chi2=18.67, P=.000016, odds ratio = 1.88 [95% CI 1.41--2.51]). Our results suggest that these eight SNPs in selectin genes may be useful for screening populations susceptible to the IgAN phenotype that involves interstitial infiltration.
authors.affiliation: Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takei
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yozo
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Takeoka
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ito
authors.forename: Kazuho
authors.initials: K
authors.lastname: Honda
authors.forename: Keiko
authors.initials: K
authors.lastname: Uchida
authors.forename: Ken
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Ujiie
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagane
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nihei
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D019040:E-Selectin / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D019041:L-Selectin / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D019040:E-Selectin; D019041:L-Selectin