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 signifi-cantly associated with fetal allele G*0106 only in multigravid pregnancies (P 5 0.002, OR 5 5.0, 95 % CI 5 1.8–13.8). Among multigravid pregnancies, the frequency of PE babies heterozygous or homozygous for G*0106 was also significantly higher com-pared with normal control babies (P 5 0.002, OR5 5.4, 95 % CI 5 1.9–15.4). Multivariate analyses with adjustment for factors associated with PE revealed similar results (P 5 0.003, OR5 10.1, 95 % CI 5 2.2–46.8). Additionally, a significantly higher fre