title: Meta-analysis of the human leukocyte antigen-G (HLA-G) 14 bp insertion/deletion polymorphism as a risk factor for preeclampsia.
abstract: The non-classical major histocompatibility complex, human leukocyte antigen (HLA)-G, plays an important role in pregnancy. HLA-G mediates proper interaction between maternal immune cells and fetal trophoblasts invading the uterine wall, to ensure successful placental development and function. Several HLA-G gene variants have been shown to be associated with development of preeclampsia (PE), but the reported associations of the HLA-G 14 base pair (bp) insertion/deletion (I/D) polymorphism (rs66554220) with PE are inconsistent. In this meta-analysis of HLA-G 14 bp I/D in each member of the family triad, we estimated risk (odds ratio [OR], 95% confidence interval) of associations with PE based on nine published offspring, nine mother and three father case-control studies. No significant increased risk associations between PE and HLA-G 14 bp I/D were detected in any of the family triad members (offspring: OR = 1.08-1.21, P = 0.57-0.74; mothers: OR = 1.11-1.28, P = 0.07-0.44; fathers: OR = 1.09-1.65, P = 0.07-0.70). Of the 20 comparisons performed, 14 (70%) were non-heterogeneous and seven of these had zero heterogeneity (I(2) = 0%). Sensitivity treatment confirmed robustness for the overall lack of association for HLA-G 14 bp I/D. In subgroup analysis, significant association between HLA-G 14 bp I/D and PE was shown in offspring from primipara (OR = 1.66-1.95, P = 0.04) and European Caucasian pregnancies (OR = 1.37-2.03, P = 0.02-0.03). However, heterogeneity and sensitivity tests suggest that further investigation is needed to determine if HLA-G 14 bp I/D is involved in trophoblast HLA-G expression and PE development in these subgroups.
authors.affiliation: Center for Research and Development, Angeles University Foundation, Angeles City, 2009, Philippines.|School of Medicine, Saint Louis University, Baguio City, 2600, Philippines.
authors.forename: N
authors.identifier: http://orcid.org/0000-0003-2069-5535
authors.initials: N
authors.lastname: Pabalan
authors.affiliation: Environmental Monitoring and Reporting Branch, Biomonitoring Unit, Ontario Ministry of the Environment and Climate Change, Ontario, M9P 3V6, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Jarjanazi
authors.affiliation: Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, N-5021, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, N-7491, Norway.
authors.forename: A C
authors.initials: AC
authors.lastname: Iversen
mesh_terms: D020029:Base Pairing; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D059951:HLA-G Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D059951:HLA-G Antigens
keywords: human leukocyte antigen-G; meta-analysis; polymorphism; preeclampsia