Association between single-nucleotide polymorphisms in selectin genes and immunoglobulin A nephropathy.
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.
Takei
Takashi
T
Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo Women's Medical University, Tokyo, Japan.
Iida
Aritoshi
A
Nitta
Kosaku
K
Tanaka
Toshihiro
T
Ohnishi
Yozo
Y
Yamada
Ryo
R
Maeda
Shiro
S
Tsunoda
Tatsuhiko
T
Takeoka
Sachiyo
S
Ito
Kyoko
K
Honda
Kazuho
K
Uchida
Keiko
K
Tsuchiya
Ken
K
Suzuki
Yasushi
Y
Fujioka
Tomoaki
T
Ujiie
Takashi
T
Nagane
Yutaka
Y
Miyano
Satoru
S
Narita
Ichiei
I
Gejyo
Fumitake
F
Nihei
Hiroshi
H
Nakamura
Yusuke
Y
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
D019040:E-Selectin; D019041:L-Selectin