| | |  | | | | Record from Web of Science® | | | | | | |
| Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele |
|
|
| Author(s): Morahan G, Huang DX, Ymer SI, Cancilla MR, Stephen K, Dabadghao P, Werther G, Tait BD, Harrison LC, Colman PG |
| Source: NATURE GENETICS Volume: 27 Issue: 2 Pages: 218-221 Published: FEB 2001 |
| Times Cited: 172 References: 29 |
| Abstract: Type 1 diabetes (T1D; or insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease with both genetic and environmental components. In addition to the human leukocyte antigen (HLA) complex, the single major genetic contributor of susceptibility(1), an unknown number of other unidentified genes are required to mediate disease. Although many loci conferring susceptibility to T1D have been mapped(2), their identification has proven problematic(3) due to the complex nature of this disease. Our strategy for finding T1D susceptibility genes has been to test for human homologues of loci implicated in diabetes-prone NOD (non-obese diabetic) mice, together with application of biologically relevant stratification methods(4). We report here a new susceptibility locus, IDDM18 located near the interleukin-12 (IL-12)p40 gene, IL12B. Significant bias in transmission of IL12B alleles was observed in affected sibpairs and was confirmed in an independent cohort of simplex families. A single base change in the 3' UTR showed strong linkage disequilibrium with the T1D susceptibility locus. The IL12B 3' UTR alleles showed different levers of expression in cell lines. Variation in IL-12p40 production may influence T-cell responses crucial for either mediating or protecting against this and other autoimmune diseases. |
| Document Type: Article |
| Language: English |
| Reprint Address: Morahan, G (reprint author), Walter & Eliza Hall Inst Med Res, PO Royal Melbourne Hosp, Parkville, Vic Australia |
Addresses:
1. Walter & Eliza Hall Inst Med Res, Parkville, Vic Australia
2. Royal Childrens Hosp, Dept Endocrinol, Melbourne, Vic Australia
3. Royal Melbourne Hosp, Australian Red Cross Blood Serv, Victorian Transplantat & Immunogenet Serv, Rotary Bone Marrow Res Ctr, Melbourne, Vic Australia |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 399XH |
| ISSN: 1061-4036 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |