A 212-kb region on chromosome 6q25 containing the TAB2 gene is associated with susceptibility to type 1 diabetes.
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.
Owerbach
David
D
Molecular Diabetes and Metabolism Section and the Harry B. and Aileen B. Gordon Diabetes Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. davido@bcm.tmc.edu
Piña
Lazaro
L
Gabbay
Kenneth H
KH
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002896:Chromosomes, Human, Pair 6; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004720:Endonucleases; D004722:Endoribonucleases; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D011506:Proteins; D012097:Repressor Proteins; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; C410585:TAB2 protein, human; D004720:Endonucleases; D004722:Endoribonucleases; C489862:ZC3H12D protein, human