Association of IL4R haplotypes with type 1 diabetes.
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.
Mirel
Daniel B
DB
Department of Human Genetics, Roche Molecular Systems, Alameda, California 94501, USA.
Valdes
Ana Maria
AM
Lazzeroni
Laura C
LC
Reynolds
Rebecca L
RL
Erlich
Henry A
HA
Noble
Janelle A
JA
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*
D019948:Receptors, Interleukin-4