title: TRAC variants associate with IgA nephropathy.
abstract: The T cell receptor alpha constant gene (TRAC) encodes the constant region of the alpha chain for the T cell receptor, and the association of its gene variants with IgA nephropathy remains controversial. The authors resequenced the gene in 100 patients with IgA nephropathy and 100 controls, tested its linkage disequilibrium pattern, constructed haplotypes, and performed association and functional studies. First, the association between TRAC variants and IgA nephropathy was tested in 704 patients and 704 controls. Next, these 704 patients were divided into two independent datasets--310 with family member(s) and 394 single patients--to test the association separately. Results showed that the gene is located in a recombination hot spot, with nine linkage disequilibrium blocks within a 6.9-kb region. There is a hypervariable region with six single-nucleotide polymorphisms (SNPs) in an 85-bp stretch in intron 1. We identified multiple SNPs and two haplotypes that associate with IgA nephropathy (P = 0.0000013-0.0096 by logistic regression for SNPs; P = 0.0003 and P = 0.0398 for haplotype associations). The family-based study replicated both haplotype findings, and the 394 single-patient case-control study replicated the association with haplotype 1 (P = 0.0033). The overtransmitted/observed haplotypes demonstrated reduced transcription activity compared with the undertransmitted/observed haplotypes. In conclusion, this study suggests an association between TRAC variants and susceptibility to IgA nephropathy.
authors.affiliation: Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Xue
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.forename: Youji
authors.initials: Y
authors.lastname: Li
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Man F
authors.initials: MF
authors.lastname: Lam
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Kar N
authors.initials: KN
authors.lastname: Lai
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D019673:Genes, T-Cell Receptor alpha; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger