TRAC Variants Associate with IgA Nephropathy
TRAC Variants Associate with IgA Nephropathy
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TRAC 变异与 IgA 肾病相关
DOI：
10.1681/asn.2008080842
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发表时间：
2009-06-01
影响因子：
13.6
通讯作者：
Wang, Yiming
中科院分区：
文献类型：
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作者：
Li, Ru;Xue, Chao;Wang, Yiming
T细胞受体α恒定基因(TRAC)编码T细胞受体α链的恒定区，其基因变异与IgA肾病的关系仍存在争议。作者对100名IgA肾病患者和100名对照进行了基因重测序，测试了其连锁不平衡模式，构建了单倍型，并进行了关联和功能研究。首先，在704名患者和704名对照中测试了TRAC变异与IgA肾病的关系。接下来，这704名患者被分成两个独立的数据集-310名有家庭成员(S)的患者和394名单身患者-以分别测试相关性。结果表明，该基因位于一个重组热点区域，在一个6.9 kb的区域内有9个连锁不平衡块。在内含子1的85个碱基上有一个含有6个单核苷酸多态(SNPs)的高变区。我们发现了多个SNPs和两个单倍型与IgA肾病相关(SNPs Logistic回归分析P=0.0000013-0.0096；单倍型关联P=0.0003和P=0.0398)。这项以家庭为基础的研究重复了两种单倍型的研究结果，而394名单患者病例对照研究重复了与单倍型1的关联(P=0.0033)。与未传输/观察到的单倍型相比，超传/观察到的单倍型的转录活性降低。综上所述，本研究提示TRAC基因变异与IgA肾病易感性有关。
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.