title: Association of IL4R haplotypes with type 1 diabetes.
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.
authors.affiliation: Department of Human Genetics, Roche Molecular Systems, Alameda, California 94501, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mirel
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Valdes
authors.forename: Laura C
authors.initials: LC
authors.lastname: Lazzeroni
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Reynolds
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005190:Family; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics*
chemical_list: D019948:Receptors, Interleukin-4