HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage.
HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique 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, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms 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 of the HLA-G1 isoforms contributes to recurrent miscarriage.
Aldrich
C L
CL
Department of Human Genetics, The University of Chicago, IL 60637, USA.
Stephenson
M D
MD
Karrison
T
T
Odem
R R
RR
Branch
D W
DW
Scott
J R
JR
Schreiber
J R
JR
Ober
C
C
D000026:Abortion, Habitual / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D012307:Risk Factors; D016896:Treatment Outcome
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I