HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage

HLA-G is a non-classical human leukocyte antigen expressed primarily in fet al tissues at the maternal-fetal interface. This expression pattern is uniq ue among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 11 3 couples with unexplained recurrent miscarriage were genotyped for seven p olymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased r isk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*01 05N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previou s miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphis ms,in the alpha -2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha -2 domain o f the HLA-G1 isoforms contributes to recurrent miscarriage.