A 212-kb region on chromosome 6q25 containing the TAB2 gene is associated with susceptibility to type 1 diabetes

被引:41
作者
Owerbach, D
Piña, L
Gabbay, KH
机构
[1] Baylor Coll Med, Dept Pediat, Mol Diabet & Metab Sect, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Pediat, Harry B & Aileen B Gordon Diabet Res Ctr, Houston, TX 77030 USA
关键词
D O I
10.2337/diabetes.53.7.1890
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The IDDM5 gene, which is identified by whole-genome searches, is located on chromosome 6q25. TAB2 (MAP3K7IP2 [mitogen-activating protein kinase kinase kinase 7 interacting protein 2]) is a potential candidate gene for type 1 diabetes because it is located on chromosome 6q25 and is involved in nuclear factor (NF)-kappaB regulation. We have conducted familial association studies using 478 families and demonstrate that a type 1 diabetes susceptibility gene resides within a 212-kb region containing the TAB2 gene (Tsp = 1.0 x 10(-2) to 4.0 x 10(-4)). No amino acid polymorphisms were detected in TAB2; however, multiple single nucleotide polymorphisms (SNPs) found within 5' untranslated, 3' untranslated, and intron regions were associated with type 1 diabetes susceptibility. Two additional genes, LOC340152, a predicted gene with currently unknown function, and SMT3, which has homology to SUMO (small ubiquitin-related modifier) were found within the 212-kb region and were associated with type 1 diabetes susceptibility. Functional studies of the three genes will be required to determine their biological relevance to type 1 diabetes. However, both TAB2 and SUMO are involved in NF-kappaB activation and may thus be involved in type 1 diabetes through apoptosis in pancreatic beta-cells.
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收藏
页码:1890 / 1893
页数:4
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