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Hum. Reprod. Advance Access published online on April 7, 2004
Human Reproduction, doi:10.1093/humrep/deh200
© 2004 by European Society of Human Reproduction and Embryology
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Received October 27, 2003
Accepted February 10, 2004

Article

A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB103 is associated with recurrent miscarriage

C. Kruse 1*, R. Steffensen 2, K. Varming 2, and O.B. Christiansen 3

1 Department of Obstetrics and Gynaecology, Aalborg Hospital, PO Box 561, DK-9100 Aalborg, Denmark; Rolighedsvej 6, DK-9400 Norresundby, Denmark
2 Department of Clinical Immunology, Aalborg Hospital, PO Box 561, DK-9100 Aalborg, Denmark
3 Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: ckruse{at}dadlnet.dk.


  Abstract

BACKGROUND: Previous studies have demonstrated an association between recurrent miscarriage (RM) and the maternal HLA-DRB101 and -DRB103 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-DRB103 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-DRB101. CONCLUSION: The HLA-DRB103 allele or genes in linkage disequilibrium with it confer susceptibility to RM.

Key words: Key words: abortion/HLA antigens/HLA class II/immunology/recurrent miscarriage


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