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Diabetes 51:3336-3341, 2002
© 2002 by the American Diabetes Association, Inc.
Brief Genetics Reports |
Association of IL4R Haplotypes With Type 1 Diabetes
1 Department of Human Genetics, Roche Molecular Systems, Alameda, California
2 Division of Biostatistics, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California
3 Children’s Hospital Oakland Research Institute, Oakland, California
We have investigated, in 282 multiplex Caucasian families (the Human Biological Data Interchange Repository), the association of type 1 diabetes with polymorphisms in the IL4R gene. IL4R encodes a subunit of the interleukin-4 receptor, a molecule critical to T-helper cell development. By genotyping eight different IL4R single-nucleotide polymorphisms (SNPs) and identifying haplotypes (complex alleles) in the multiplex type 1 diabetic families who were stratified for HLA genotype, we have observed significant evidence of linkage and association of the IL4R gene to type 1 diabetes. In particular, we have identified a specific haplotype that appears to be protective and observed that this protective effect is strongest among individuals not carrying the HLA DR3/DR4 genotype (which confers the strongest genetic risk for type 1 diabetes). These findings suggest an important role for the IL4R gene in immune-related disease susceptibility and illustrate the value of using multi-SNP haplotype information in association studies.
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