Association of HLA class I and class II alleles with susceptibility to endometriosis

Although the exact etiology of endometriosis is unclear, several lines of evidence support roles for both cell-mediated and humoral immunity in its pathogenesis. To assess the association between HLA genotypes and endometriosis, we investigated the frequencies of HLA-A, -B, -C, and -DRB1 antigens or alleles in 123 Japanese patients with endometriosis and 165 healthy women as controls. Significant positive association with endometriosis was observed for HLA-B7 (OR = 2.7, 95% CI = 1.5-5.1, p(u) = 0.0022, p(c) = 0.0440) and for Cw*0702 (OR = 2.1, 95% CI = 1.2-3.3, p(u) = 0.0026, p(c) = 0.0398). An increased frequency of DRB1*0101 was observed in endometriosis patients compared with control subjects (OR = 2.3, 95% CI = 1.2-4.4, p(u) = 0.0143), but was not statistically significant after correction for multiple comparisons. Two-locus analysis indicated that the susceptibility to endometriosis was primarily associated with B7, and that the increased frequencies of Cw*0702 and DRB1*0101 in patients reflected the linkage disequilibrium between B7 and Cw*0702 and DRB1*0101. Most of the B7 antigens were encoded by the B*0702 allele, which was in complete linkage disequilibrium with A24, Cw*0702, and DRB1*0101. Therefore, our results indicated that the HLA-A24-B*0702-Cw*0702-DRB1*0101 haplotype was associated with endometriosis susceptibility. Our findings may provide an important clue to elucidating the pathogenesis of endometriosis.