Maternal HLA-DR, HLA-DQ, and HLA-DP loci are linked with altered risk of recurrent pregnancy loss in Lebanese women: A case-control study.

PROBLEM: We investigated the association between idiopathic recurrent pregnancy loss (RPL) and HLA-DPB1, HLA-DQB1, and HLA-DRB1 alleles and DPB1-DQB1-DRB1 haplotypes.

METHOD OF STUDY: Case-control retrospective study involved 93 Lebanese women with unexplained RPL, and 113 multiparous Lebanese women with two or more successful pregnancies, and no miscarriages who served as controls. DPB1, DQB1, and DRB1 genotyping was performed by PCR-SSP.

RESULTS

Expected and observed DRB1, DQB1, and DPB1 frequencies were comparable, and HLA genotype frequencies were in Hardy-Weinberg equilibrium. Significantly higher frequencies of DRB1*04:01:01 and DRB1*08:01:01, and decreased DRB1*07:01:01 frequency were seen in RPL cases than in controls. On the other hand, the distribution of DQB1 alleles was comparable between cases and control groups. Significantly lower frequencies of DPB1*04:01:01 and DPB1*14:01:01 were seen in women with RPL than control subjects. While the frequency DPB1*02:01:01 was markedly higher in RPL cases than in controls, the difference was not significant. DPB1-DQB1-DRB1 haplotype analysis identified haplotype DPB1*04:01:01-DQB1*03:02:01-DRB1*04:01:01 to be positively associated, while haplotype DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 to be negatively associated with RPL. Of these two haplotypes, only DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 remained significant after correction for multiple tests (Pc  = .0008).

CONCLUSION

Our results confirm an association of select DRB1 and DPB1 alleles with RPL in Lebanese women, and the first to identify DPB1-DQB1-DRB1 linked with altered RPL susceptibility, further highlighting the immunological/inflammatory nature of RPL.