HLA-DR and HLA-DQ Allele Associations with Idiopathic Recurrent Pregnancy Loss in Azerbaijani Women

Background/Objectives: HLA class II molecules play a pivotal role in maternal–fetal immune tolerance; however, their contribution to recurrent pregnancy loss (RPL) appears population-specific. This study investigated associations between HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles and idiopathic RPL in Azerbaijani women. Methods: A case–control study included 125 women with idiopathic RPL and 138 ethnically matched fertile controls. All participants had normal karyotypes and no identifiable anatomical, endocrine, or other established causes of pregnancy loss. HLA class II genotyping was performed using SSP-PCR. Allele frequencies were compared using chi-square or Fisher’s exact tests, as appropriate. Hardy–Weinberg equilibrium was assessed in controls using the chi-square goodness-of-fit test. Benjamini–Hochberg FDR correction was applied across all 25 allele-level comparisons. Results: Several alleles showed nominal associations with RPL before multiple-testing correction, including HLA-DRB1*04, DRB1*11, DRB1*15, HLA-DQB1*03, DQB1*05, HLA-DQA1*01, DQA1*05, and DQA1*06. After FDR correction, HLA-DQB1*05 (p = 0.004, q = 0.050; OR = 1.95, 95% CI: 1.24–3.07) showed a borderline association with increased RPL susceptibility, whereas HLA-DQB1*02 (p = 0.004, q = 0.050; OR = 0.54, 95% CI: 0.35–0.82) showed a borderline protective association. The remaining nominal associations did not remain significant (q > 0.05). Conclusions: HLA-DQB1*05 and DQB1*02 showed borderline associations with idiopathic RPL in Azerbaijani women after FDR correction. These findings should be interpreted cautiously and validated in larger, independent, multi-ethnic cohorts.