Association of IL4R Haplotypes With Type 1 Diabetes
- Daniel B. Mirel1,
- Ana Maria Valdes1,
- Laura C. Lazzeroni2,
- Rebecca L. Reynolds1,
- Henry A. Erlich13 and
- Janelle A. Noble3
- 1Department of Human Genetics, Roche Molecular Systems, Alameda, California
- 2Division of Biostatistics, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California
- 3Children’s Hospital Oakland Research Institute, Oakland, California
Abstract
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.
Footnotes
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Address correspondence and reprint requests to Henry A. Erlich, Roche Molecular Systems, 1145 Atlantic Ave., Alameda CA 94501. E-mail: henry.erlich{at}roche.com.
Received for publication 8 February 2002 and accepted in revised form 26 July 2002.
HBDI, Human Biological Data Interchange; IBD, identity by descent; IL4, interleukin-4; LD, linkage disequilibrium; LOD, logarithm of odds; OR, odds ratio; SNP, single-nucleotide polymorphism; TDT, transmission disequilibrium test.
- DIABETES
