A study of HLA‐DR and ‐DQ alleles in 588 patients and 562 controls confirms that HLA‐DRB1*03 is associated with recurrent miscarriage.

BACKGROUND: Previous studies have demonstrated an association between recurrent miscarriage (RM) and the maternal HLA‐DRB1*01 and ‐DRB1*03 alleles. The primary aim of the present study was to confirm or reject the hypothesis about this association in a larger case–control study. METHODS: HLA‐DRB1, ‐DQA1 and ‐DQB1 genotyping was carried out by the PCR–sequence‐specific primer (SSP) method in 354 patients with unexplained RM and 202 fertile controls. These results were combined with the results from a previous study of 234 RM patients and 360 controls. RESULTS: The prevalence of patients with HLA‐DRB1*03 was significantly increased compared with controls [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.1–1.9, P = 0.01, P corrected for the number of comparisons (Pc) = 0.02]. In patients with at least four previous miscarriages or with secondary RM, the association became even stronger (OR = 1.8, 95% CI = 1.3–2.5, P = 0.0005, Pc = 0.004; and OR = 1.8, 95% CI = 1.3–2.5, P = 0.0007, Pc = 0.006, respectively). There was no significant differerence between patients and controls with regard to HLA‐DRB1*01. CONCLUSION: The HLA‐DRB1*03 allele or genes in linkage disequilibrium with it confer susceptibility to RM. [ABSTRACT FROM AUTHOR]