title: A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1*03 is associated with recurrent miscarriage.
abstract: 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 difference between patients and controls with regard to HLA-DRB1*01.
  
  
  CONCLUSIONS
  The HLA-DRB1*03 allele or genes in linkage disequilibrium with it confer susceptibility to RM.
authors.affiliation: Department of Obstetrics and Gynaecology, Aalborg Hospital, Denmark. ckruse@dadlnet.dk
authors.forename: C
authors.initials: C
authors.lastname: Kruse
authors.forename: R
authors.initials: R
authors.lastname: Steffensen
authors.forename: K
authors.initials: K
authors.lastname: Varming
authors.forename: O B
authors.initials: OB
authors.lastname: Christiansen
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains