Human leukocyte antigen (HLA)-G during pregnancy part II: associations between maternal and fetal HLA-G genotypes and soluble HLA-G

TY - JOUR

T1 - Human leukocyte antigen (HLA)-G during pregnancy part II

T2 - associations between maternal and fetal HLA-G genotypes and soluble HLA-G

AU - Dahl, Mette

AU - Klitkou, Louise

AU - Christiansen, Ole B

AU - Djurisic, Snezana

AU - Piosik, Zofia Maria

AU - Skovbo, Peter

AU - Møller, Anna Margrethe

AU - Steffensen, Rudi

AU - Hviid, Thomas Vauvert F

N1 - Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

PY - 2015/4

Y1 - 2015/4

N2 - Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.

AB - Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.

KW - 3' Untranslated Regions

KW - Abortion, Habitual

KW - Alleles

KW - DNA Mutational Analysis

KW - Female

KW - Fetal Blood

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Gestational Age

KW - HLA-G Antigens

KW - Histocompatibility

KW - Humans

KW - Polymorphism, Genetic

KW - Pre-Eclampsia

KW - Pregnancy

KW - Journal Article

U2 - 10.1016/j.humimm.2015.01.015

DO - 10.1016/j.humimm.2015.01.015

M3 - Journal article

C2 - 25637667

SN - 0198-8859

VL - 76

SP - 260

EP - 271

JO - Human Immunology

JF - Human Immunology

IS - 4

ER -