Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease.
Pre-eclampsia is a disorder of human pregnancy occurring in 5-10% of all births, and represents the leading cause of infant morbidity and mortality and maternal death. In pre-eclampsia, invasion of fetal trophoblasts into maternal arteries during early pregnancy is shallow or absent. Here we examined the hypothesis that HLA-G, a non-classical class I HLA expressed in cytotrophoblasts, may act as a key gene in pre-eclampsia. We analysed HLA-G at the level of transcription and genotyped a silent CAC-CAT polymorphism in exon 3 and a 14-bp insertion/deletion in the 3' untranslated region. A deficit in levels of the HLA-G3 transcript was observed in mild pre-eclampsia compared to normal placentas. The distribution of HLA-G polymorphisms was different between normal and pre-eclampsia samples. A correlation between the alteration in transcription of the HLA-G gene and certain HLA-G genotypes was also observed. Thus we provide the first evidence for a possible role of HLA-G in genetic susceptibility to, and pathogenesis of pre-eclampsia.
O'Brien
M
M
CEA, Service de Recherches en Hémato-immunologie, DSV/DRM, Hôpital Saint-Louis, Institut d'Hématologie, Paris, France.
McCarthy
T
T
Jenkins
D
D
Paul
P
P
Dausset
J
J
Carosella
E D
ED
Moreau
P
P
D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D020073:Gravidity; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010298:Parity; D010920:Placenta / Q000502:physiology / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I