Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies.
Pre-eclampsia (PE) is a leading cause of maternal and fetal mortality and morbidity. Structural or functional alterations of human leukocyte antigen (HLA)-G present at the maternal-fetal interface may predispose women to PE. We tested the HLA-G gene for association with PE in a case-control study of 83 PE and 240 normotensive Malay women. HLA-G was amplified in a single-tube multiplex-PCR reaction and genotyped for 18 single nucleotide polymorphisms (SNPs) by multiplex-minisequencing. Case-control comparisons were performed, and associations with disease were expressed as odds ratios (ORs). Risk for PE was significantly associated with fetal allele G*0106 only in multigravid pregnancies (P = 0.002, OR = 5.0, 95% CI = 1.8-13.8). Among multigravid pregnancies, the frequency of PE babies heterozygous or homozygous for G*0106 was also significantly higher compared with normal control babies (P = 0.002, OR = 5.4, 95% CI = 1.9-15.4). Multivariate analyses with adjustment for factors associated with PE revealed similar results (P = 0.003, OR = 10.1, 95% CI = 2.2-46.8). Additionally, a significantly higher frequency of fetal-maternal G*0106 genotype mismatch was observed in PE compared with normal multigravid pregnancies (P = 0.001, OR = 9.6, 95% CI = 2.4-38.7). Thus, paternal HLA-G G*0106 contribution significantly increases risk for PE in multigravidas who do not carry this allele, potentially mediated by a gradual maternal alloimmune response to repeated exposure to the paternal HLA-G variant.
Tan
Chia Yee
CY
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore, Singapore.
Ho
Julia F V
JF
Chong
Yap Seng
YS
Loganath
Annamalai
A
Chan
Yiong Huak
YH
Ravichandran
Jeganathan
J
Lee
Caroline G
CG
Chong
Samuel S
SS
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D020073:Gravidity / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D040582:Inheritance Patterns; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors
D006680:HLA Antigens; D059951:HLA-G Antigens; C530755:HLA-G*01:06 antigen; D015395:Histocompatibility Antigens Class I