A possible mechanism for non replication of allelic association between a SNP of the human beta T cell receptor and autoimmune diseases

Gene polymorphisms, in particular single nucleotide polymorphisms (SNP), have been associated to multi-factorial diseases such as cancer, inflammation and autoimmunity. Indeed for some autoimmune diseases it has been possible to identify critical residues that play a major role in susceptibility to disease. The association of a common T/C polymorphism in the promoter region of the beta 2 constant chain of the T cell receptor with autoimmune diseases as insulin-dependent diabetes, autoimmune hepatitis, IgA nephropathy, membranous nephropathy, Graves’disease and Hashimoto’s thyroiditis, was described in the ninenties. These reports have not be confirmed in last few years. Indeed an interesting difference of allelic frequency in male e female was observed in some studies, this finding led us to make an allele frequency study of this single nucleotide polymorphism between sexes in a new series of patients. We studied 165 subjects, 80 males and 85 females, and we found a significant difference between sexes especially for the CC homozygous genotype: 34% of females versus 14% of males (p = 0.008). If the higher frequency in females of CC homozygous genotype (that is associated with an increased risk of autoimmune diseases) would be confirmed in normal population, this could be a explanation of the controversial results obtained in association study made between this SNP and autoimmune disease.