TY - JOUR
T1 - The 3'-untranslated region of the HLA-G gene in relation to pre-eclampsia: revisited
AU - Larsen, M H
AU - Hylenius, S
AU - Andersen, Anne-Marie Nybo
AU - Hviid, Thomas
PY - 2010/3
Y1 - 2010/3
N2 - 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, PC = 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.
AB - 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, PC = 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.
U2 - 10.1111/j.1399-0039.2009.01435.x
DO - 10.1111/j.1399-0039.2009.01435.x
M3 - Journal article
C2 - 20070604
SN - 2059-2302
VL - 75
SP - 253
EP - 261
JO - HLA
JF - HLA
IS - 3
ER -