Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage

TY - JOUR

T1 - Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage

AU - Kolte, Astrid M

AU - Steffensen, Rudi

AU - Nielsen, Henriette S

AU - Hviid, Thomas V

AU - Christiansen, Ole B

N1 - Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

PY - 2010/5

Y1 - 2010/5

N2 - A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more siblings suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was significantly increased in probands with RM (p = 0.05). The increased compatibility between probands and their mothers for maternal G14 ins positive haplotypes suggests that maternal-fetal compatibility for chromosomal segments adjacent to HLA-G locus is a risk factor for female offspring to experience RM in their later reproductive life.

AB - A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more siblings suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was significantly increased in probands with RM (p = 0.05). The increased compatibility between probands and their mothers for maternal G14 ins positive haplotypes suggests that maternal-fetal compatibility for chromosomal segments adjacent to HLA-G locus is a risk factor for female offspring to experience RM in their later reproductive life.

KW - Abortion, Habitual

KW - Female

KW - Genetic Predisposition to Disease

KW - HLA Antigens

KW - HLA-A Antigens

KW - HLA-B Antigens

KW - HLA-DR Antigens

KW - HLA-DRB1 Chains

KW - HLA-G Antigens

KW - Haplotypes

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Linkage Disequilibrium

KW - Pedigree

KW - Pregnancy

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.humimm.2010.02.001

DO - 10.1016/j.humimm.2010.02.001

M3 - Journal article

C2 - 20149831

SN - 0198-8859

VL - 71

SP - 482

EP - 488

JO - Human Immunology

JF - Human Immunology

IS - 5

ER -