Maternal and fetal human leukocyte antigen class Ia and II alleles in severe preeclampsia and eclampsia.
A line of investigations indicate that genes in the human leukocyte antigen (HLA) complex are involved in a successful acceptance of the semiallogeneic fetus during pregnancy. In this study, associations between specific HLA class Ia (HLA-A and -B) and class II (HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) alleles and the risk of developing severe preeclampsia/eclampsia were investigated in a detailed and large-scale study. In total, 259 women diagnosed with severe preeclampsia or eclampsia and 260 matched control women with no preeclampsia, together with their neonates, were included in the study. HLA genotyping for mothers and neonates was performed using next-generation sequencing. The HLA-DPB1*04:01:01G allele was significantly more frequent (Pc=0.044) among women diagnosed with severe preeclampsia/eclampsia compared with controls, and the DQA1*01:02:01G allele frequency was significantly lower (Pc=0.042) among newborns born by women with severe preeclampsia/eclampsia compared with controls. In mothers with severe preeclampsia/eclampsia, homozygosity was significantly more common compared with controls at the HLA-DPB1 locus (Pc=0.0028). Although the current large study shows some positive results, more studies, also with a functional focus, are needed to further clarify a possible role of the classical HLA genes in preeclampsia.
Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital (Roskilde) and University of Copenhagen, Roskilde, Denmark.
J
J
Emmery
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
R
R
Hachmon
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
C W
CW
Pyo
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
W C
WC
Nelson
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
D E
DE
Geraghty
Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
A M N
AM
Andersen
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.|Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
M
M
Melbye
Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital (Roskilde) and University of Copenhagen, Roskilde, Denmark.
T V F
TV
Hviid
D000328:Adult; D004461:Eclampsia / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006681:HLA-D Antigens