Gene polymorphisms, in particular single nucleotide polymorphisms (SNPs), have been associated to multifactorial 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 diseases. 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, such as insulin-dependent diabetes, autoimmune hepatitis, IgA nephropathy, membranous nephropathy, Graves' disease and Hashimoto's thyroiditis, was described in the 1990 s. These reports have not been confirmed in the last few years. We also failed in a previous study to detect any difference between 70 normal subjects and 70 patients with primary biliary cirrhosis; however, we found a difference in allelic frequency between males and females. 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 vs. 14% of males (P = 0.008). If the higher frequency of CC homozygous genotype (that is associated with an increased risk of autoimmune diseases) in females would be confirmed in normal population, this could be an explanation of the controversial results obtained by association studies made between this SNP and autoimmune diseases.