title: Associations between fetal HLA-G genotype and birth weight and placental weight in a large cohort of pregnant women - Possible implications for HLA diversity.
abstract: Birth weight and placental weight are crucial parameters for the survival of fetuses and newborns in mammals. High variation in the MHC is important for an effective adaptive immune response. The maternal immune system must be controlled in relation to the semi-allogenic fetus. The immunoregulatory HLA/MHC class Ib gene, HLA-G, is strongly expressed on extravillous trophoblast cells. We investigated birth weight and placental weight of the newborns in mothers heterozygous for an HLA-G 14bp insertion (Ins)/deletion (Del) gene polymorphism. Separate analyses for pregnancies without preeclampsia (n=185), pregnancies complicated by preeclampsia (n=101), and both groups combined, were performed. Interestingly, we observed the highest mean birth weight and placental weight in homozygous 14bp Del/Del newborns, and the lowest in 14bp Ins/Ins newborns (P=0.008 and P=0.009). The 14bp Del/Del genotype is also associated with high expression of HLA-G on the trophoblast membrane. In theory, fetuses and newborns with intermediate weights and sizes would be an optimal compromise for both the fetus/father and the mother compared with very high and low weights. If such fetuses/newborns more often are heterozygous at the HLA-G gene locus, then newborns with two distinct HLA haplotypes are favored, leading to a higher degree of HLA diversity. The results of the study may indicate that a compromise between an intermediate birth weight and placental weight, induction of maternal tolerance by a fetal-derived non-polymorphic HLA class Ib molecule, and favoring of HLA heterozygous offspring, have evolved in humans.
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital and University of Copenhagen, DK-4000 Roskilde, Denmark.
authors.forename: Johanne
authors.initials: J
authors.lastname: Emmery
authors.affiliation: Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; Department of Obstetrics and Gynecology, Aalborg University Hospital, 9000 Aalborg, Denmark.
authors.forename: Ole B
authors.initials: OB
authors.lastname: Christiansen
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital and University of Copenhagen, DK-4000 Roskilde, Denmark.
authors.forename: Line Lynge
authors.initials: LL
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital and University of Copenhagen, DK-4000 Roskilde, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Dahl
authors.affiliation: Department of Obstetrics and Gynecology, Aalborg University Hospital, 9000 Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Skovbo
authors.affiliation: Department of Obstetrics and Gynecology, Aalborg University Hospital, 9000 Aalborg, Denmark.
authors.forename: Anna Margrethe
authors.initials: AM
authors.lastname: Møller
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, 9000 Aalborg, Denmark.
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital and University of Copenhagen, DK-4000 Roskilde, Denmark. Electronic address: tvh@regionsjaelland.dk.
authors.forename: Thomas Vauvert F
authors.initials: TVF
authors.lastname: Hviid
mesh_terms: D056704:Adaptive Immunity; D001724:Birth Weight; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005865:Gestational Age; D059951:HLA-G Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009929:Organ Size; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D017384:Sequence Deletion / Q000235:genetics*; D023001:Transplantation Tolerance; D014327:Trophoblasts / Q000378:metabolism*; D066253:Vascular Remodeling
chemical_list: D059951:HLA-G Antigens
keywords: Birth weight; Genotype; HLA-G; MHC diversity; Pregnancy