Studies of RFLP-inferred HLA-DR-DQ haplotypes in Danish women with recurrent fetal losses.
Results of HLA-DR and -DQ typing by RFLP in 152 unrelated women with at least 3 unexplained fetal losses were compared with those of 210 normal controls. The overall distribution of DR-DQ phenotypes did not differ significantly between patients and controls. In a subgroup of 59 patients having had at least 4 fetal losses, a significantly higher number of patients than controls were DRw17,DQw2-positive (RR = 2.9, pcorrected less than 0.02). DR-DQ haplotypes which carry DQB1 alleles encoding an amino acid other than aspartic acid at codon 57 in the second exon (non-Asp57 haplotypes) have been reported to confer susceptibility to several immunologically-mediated diseases. We found that the total frequency of non-Asp57 haplotypes (other than DR7,DQw2 which has unique features) was significantly increased in patients (50.0%) compared with controls (39.3%) (p less than 0.005). In the total group of patients and in the group with at least 4 fetal losses, 22.4% and 32.2% respectively were homozygous non-Asp57/non-Asp57 compared with 13.3% among controls (RR = 1.9, p less than 0.025 and RR = 3.1, p less than 0.001, respectively). The results suggest that DRw17,DQw2 confers susceptibility to suffer recurrent fetal losses. However, it is possible that the HLA-associated susceptibility may be primarily conferred by DQ molecules lacking aspartic acid at codon 57 in the DQ beta chain.
Department of Clinical Immunology, Aalborg Hospital, Denmark.
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Christiansen
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Mathiesen
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Husth
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Jersild
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Grunnet
D000026:Abortion, Habitual / Q000235:genetics* / Q000276:immunology; D000328:Adult; D003718:Denmark; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics* / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D006239:Haplotypes; D006801:Humans; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D044465:White People / Q000235:genetics
D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C072625:HLA-DRw17 antigen