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 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.
Kruse
C
C
Department of Obstetrics and Gynaecology, Aalborg Hospital, Denmark. ckruse@dadlnet.dk
Steffensen
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R
Varming
K
K
Christiansen
O B
OB
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
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