Endocrine Abstracts

The functional interleukin-4 receptor is a heterodimeric complex composed of the IL-4 receptor alpha chain and the common cytokine gamma chain. The interleukin-4 receptor (IL-4R) gene is located on human chromosome 16p12.1-11.2. A polymorphism at codon 50 of the alpha chain alters the receptor response to the Th2 cytokine interleukin-4 (IL-4). The allele with the amino acid isoleucine at position 50 (Ile50) upregulates receptor activity in response to binding with IL-4 compared with the allele with valine at the same position (Val50). IL-4 is an immunoregulatory cytokine and plays a central role in the regulation of B cell and T cell immune responses. The Ile50Val polymorphism has previously been reported to be associated with asthma, atopy and systemic lupus erythematosus in case-control studies. It is well documented that common susceptibility genes are shared between different autoimmune diseases and therefore we have studied the Ile50Val polymorphism in a case-control data set of patients with Graves' disease. Genomic DNA from 641 Graves' index cases and 563 control subjects of British white Caucasian origin was amplified using polymerase chain reaction (PCR) and Msl1 restriction enzyme was used to digest the 421 base pair (bp) product. A 331-bp band was visualised in those who were homozygous for the isoleucine allele (I/I) and a 265-bp band in those who were homozygous for the valine allele (V/V); both bands were visible in heterozygous individuals (I/V). Using the Chi² test no significant differences in genotype frequencies were found between the Graves' cases and the control subjects despite power >99.999% to detect an effect with a p value of 0.001 (Chi² = 0.204, p = 0.903). These data suggest that the IL-4R gene is not a susceptibility locus for Graves' disease in the UK.