The 3'-untranslated region of the HLA-G gene in relation to pre-eclampsia: revisited.
Abnormal human leukocyte antigen G (HLA-G) expression may be involved in pre-eclampsia. A 14 bp insertion/deletion polymorphism exists in exon 8 of the HLA-G gene. Fetal +14/+14 bp HLA-G genotype may predispose to pre-eclampsia in the mother. Other polymorphisms, besides the 14 bp polymorphism (rs66554220), in the 3'-untranslated region (3'-UTR) (exon 8) of the HLA-G gene might be associated with severe pre-eclampsia, especially in primiparas. By haplotype-specific polymerase chain reaction amplification and DNA sequence analysis in the offspring from 50 pre-eclamptic cases and 85 controls (35 and 58 primiparas), 4 single nucleotide polymorphisms (SNPs) were detected in exon 8 of the HLA-G gene [SNP2995 (rs1710), SNP3127 (rs1063320), SNP3172 (rs9380142), and SNP3181 (rs1610696)]. Complete linkage disequilibrium between the +14 bp allele and three of the SNPs (SNP2995, SNP3127, and SNP3172) were observed. Two of the polymorphisms (SNP3172 and SNP3181) were located right before and after an AUUUA-pentamer sequence; AU-rich sequences seem to be involved in mRNA stability. However, only the genotypes of the earlier showed 14 bp polymorphism and the SNP3127 (with a C to G substitution; P = 0.008, P(C) = 0.04) were significantly associated with severe pre-eclampsia in primiparas. In conclusion, this study indicates that the +14 bp HLA-G allele defines a nearly unique exon 8 haplotype, and fetuses homozygous for this haplotype [SNP 2995(C)/SNP 3127(G)/SNP 3172(A)/SNP 3181(G)/+14 bp] are associated with severe pre-eclampsia in primiparas.
Larsen
M H
MH
Department of Clinical Biochemistry, Roskilde University Hospital, Roskilde, Denmark.
Hylenius
S
S
Andersen
A-M Nybo
AM
Hviid
T V F
TV
D020413:3' Untranslated Regions; D000483:Alleles; D001483:Base Sequence; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D016254:Mutagenesis, Insertional; D010298:Parity / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D017384:Sequence Deletion
D020413:3' Untranslated Regions; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I