title: Maternal homozygocity for a 14 base pair insertion in exon 8 of the HLA-G gene and carriage of HLA class II alleles restricting HY immunity predispose to unexplained secondary recurrent miscarriage and low birth weight in children born to these patients.
abstract: Homozygous carriage of a 14 base pair (bp) insertion in exon 8 of the HLA-G gene may be associated with low levels of soluble HLA-G and recurrent miscarriage (RM). We investigated the G14bp insertion(ins)/deletion(del) polymorphism in 339 women with unexplained RM and 125 control women. In all patients and patients with secondary RM after a firstborn boy, 19.2% and 23.9%, respectively, were G14bp ins/ins compared with 11.2% of controls (p<0.05 and p<0.01). Among secondary RM patients with a firstborn boy, G14bp del/del and no carriage of an HLA class II (HYrHLA) allele restricting immunity against male-specific minor HY antigens was found less often than in controls (p<0.05) whereas G14bp ins/ins and carriage of HYrHLA predisposed (p<0.08) to this clinical entity. The mean birth weight of firstborn boys born to G14bp ins positive secondary RM patients was significantly lower than expected (p<0.001) but only in carriers of HYrHLA alleles (p<0.01). In conclusion, homozygosity for G14bp ins predisposes to RM. The combination of G14 ins homozygosity and carriage of HYrHLA predisposes to secondary RM in women with a firstborn boy and negatively affects birth weight in these boys.
authors.affiliation: Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. olbc@rn.dk
authors.forename: Ole B
authors.initials: OB
authors.lastname: Christiansen
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Kolte
authors.forename: Mette
authors.initials: M
authors.lastname: Dahl
authors.forename: Elisabeth C
authors.initials: EC
authors.lastname: Larsen
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.forename: Henriette S
authors.initials: HS
authors.lastname: Nielsen
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Hviid
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics* / Q000276:immunology; D000483:Alleles; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006182:H-Y Antigen / Q000276:immunology; D059951:HLA-G Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007109:Immunity; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics; D011110:Polymorphism, Genetic; D011485:Protein Binding
chemical_list: D006182:H-Y Antigen; D059951:HLA-G Antigens; D000949:Histocompatibility Antigens Class II