Conditional ETDT analysis of the Human Leukocyte Antigen region in type 1 diabetes

Annals of Human Genetics - Tập 64 Số 3 - Trang 215-221 - 2000
Bobby P. C. Koeleman1, Mathias Herr1, Population Zavattari2, Frank Dudbridge1, Received March3, D. K. G. Campbell3, A. Barnett4, Stephen C. Bain4, A Mulargia5, Miriam Loddo5, William Amos6, Francesco Cucca2, John A. Todd1
1Wellcome Trust Centre for Molecular Mechanisms in Disease, University of Cambridge, UK.
2Department of Pediatrics, S. Michele Hospital, Via Peretti, Cagliari, Sardinia, Italy
3MRC Immunochemistry Unit, Oxford, UK
4Department of Medicine, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK
5Servizio di Diabetologia Pediatrica, Ospedale S.Michele, Via Peretti Cagliari, Sardinia, Italy
6Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK

Tóm tắt

Several studies have indicated that additional genes in the major histocompatibility complex (MHC) region, other than the class II genes HLA‐DQB1 and ‐DRB1 (the IDDM1 locus), may contribute to susceptibility and resistance to type 1 diabetes. The relative magnitude of these non‐ DR/DQ effects is uncertain and their map location is unknown owing to the extraordinary linkage disequilibrium that extends over the 3.5 Mb of the MHC. The homozygous parent test has been proposed as a method for detection of additional risk factors conditional on HLA‐DQB1 and ‐DRB1. However, this method is inefficient since it uses only parents homozygous for the primary disease locus, the DQB1‐DRB1 haplotype. To overcome this limitation, Conditional ETDT was used in the present report to test for association conditional on the DQB1‐DRB1 haplotype, thereby allowing all parents to be included in the analysis. First, we confirm in UK and Sardinian type 1 diabetic families that allelic variation at HLA‐DRB1 has a very significant effect on the association of DQB1 and vice versa. The Conditional ETDT was then applied to the HLA TNF (tumour necrosis factor) region and microsatellite marker D6S273 region, both of which have been reported to contribute to IDDM1 independent of the HLA‐DQB1‐DRB1 genes. We found no evidence for a major role for either of these two regions in IDDM1.

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Annals of Human Genetics

Tập 64 Số 3

215-221

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