Untranslated Region Of HLA-G Gene Research Articles

The HLA-G 14-bp insertion/deletion polymorphism is associated with chronic hepatitis B in Southern Brazil: A case-control study

There is growing evidence that the non-classical HLA-G has a role in the process of the immune response against pathogens, including HBV and HIV. Previous studies demonstrated that a 14-bp insertion/deletion (indel) polymorphism at 3′-untranslated region of HLA-G gene interferes in the mRNA stability and expression. The present study aimed to evaluate the association of the 14-bp indel polymorphism (rs371194629) with HBV infection in chronic hepatitis B (CHB) mono-infected and HBV/HIV co-infected patients from Southern Brazil. A total of 817 individuals were analyzed, including 357 CHB patients, 134 HBV/HIV co-infected patients and 326 healthy controls. The 14-bp indel polymorphism was analyzed by DNA amplification using PCR. Logistic regression models were performed to compute adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs). To control for multiple comparisons, the Bonferroni correction was applied to the p-values. The 14-bp Ins allele was observed in 47.6% of the CHB mono-infected patients and in 41.6% of the controls (aOR = 1.33; 95% CI: 1.05–1.60; p = 0.02; pcorrected = 0.08). The results also showed that the 14-bp Ins/Ins genotype was present in 21.8% of the CHB mono-infected patients and in 12.9% of the controls (aOR = 1.91; 95% CI: 1.21–3.01; p < 0.01; pcorrected = 0.02). There was significant association between the 14-bp indel and CHB monoinfection, but not in HBV/HIV co-infection. In conclusion, the 14-bp indel polymorphism was associated with CHB in this specific population.

Association of three polymorphisms in the 3' untranslated region of the HLA-G gene with systemic lupus erythematosus in a population from Yunnan

To assess the association of three polymorphisms (14-bpINS/DEL, +3035C/T and +3142C/G) in the 3' untranslated region (3'UTR) of HLA-G gene and systemic lupus erythematosus (SLE) in Yunnan. A case-control study has been carried out on 206 SLE patients and 212 healthy controls. Genotypes of 14-bpINS/DEL (rs1704), +3035C/T (rs17179108) and +3142C/G (rs1063320) loci of 3'UTR of the HLA-G gene were determined with DNA sequencing. Allelic and genotypic frequencies of 14-bpINS/DEL and +3142C/G did not differ significantly between the two groups (P > 0.05). The frequencies of +3035T allele was significantly higher in the SLE group compared with the control group (P < 0.01, OR=1.604, 95% CI: 1.186-2.169). With a dominant inheritance model, the odd ratio of dominant genotype (CT+TT) was 2.004 (95% CI: 1.345-2.987, P=0.0006) in the SLE group. The 14-bpINS/DEL and +3142C/G polymorphisms in the 3'UTR of the HLA-G gene are not associated with susceptibility to SLE in Yunnan, whilst the T allele of +3035C/T may be a risk factor for SLE.

HLA-G 14bp polymorphism on HIV-1 perinatal transmission (P3041)

Abstract Background/aims: HLA-G is expressed at maternal-fetal interface and is strongly involved on maternal-fetal tolerance. The 3' untranslated region of HLA-G gene presents an insertion (INS) and/or deletion (DEL) of a 14bp fragment, which is associated with stability and expression levels of HLA-G mRNA. The aim of this study was to analyze the hypothesis that the 14bp polymorphism can influence the HIV vertical transmission. Methods: Blood samples were obtained from 49 mother-child pairs (26 pairs with and 23 without vertical transmission). All children were born from HIV-positive mothers who did not receive antiretroviral therapy during pregnancy. The 14 pp polymorphism was detected by PCR-amplified DNA using specific primers. Statistical analyses were made by Fisher's exact test. This study was approved by the local ethics committee. Results: We did not detect significant differences in allele and genotype frequencies between HIV-infected and HIV-uninfected child; however, the presence of the D/D homozygous genotype was more frequent among mothers with HIV-infected child (p=0.05). In addition, the 14pb similarity among mother and child pairs was more frequent on vertical transmission (69%) than on its absence. Conclusion: The presence of the genotype (DEL/DEL), associated with high production of HLA-G, and the similarities of the 14bp DEL/INS genotypes between mother and child may favor HIV mother to child transmission.

The genetic structure of 3′untranslated region of the HLA-G gene: polymorphisms and haplotypes

The HLA-G gene is predominantly expressed at the maternal-fetal interface. It has been associated with maternal-fetal tolerance and in the inhibition of cytotoxic T lymphocyte and natural killer cytolytic functions. At least two variations in the 3'untranslated region (UTR) of HLA-G locus are associated with HLA-G expression levels, the 14-bp deletion/insertion polymorphism and the +3142 single-nucleotide polymorphism (SNP). However, this region has not been completely characterized yet. The variability of the 3'UTR of HLA-G gene and its haplotype structure were characterized in 155 individuals from Brazil, as well as HLA-G alleles associated with each of the 3'UTR haplotype. The following eight variation sites were detected: the 14-bp polymorphism and SNPs at the positions +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and +3196C/G. Similarly, 11 different 3'UTR haplotypes were identified and several HLA-G alleles presented only one 3'UTR haplotype. In addition, a high linkage disequilibrium among the variation sites was detected, especially among the 14-bp insertion and the alleles +3142G and +3187A, all previously associated with low mRNA availability, demonstrating that their effects are not independent. The detailed analyses of 3'UTR of the HLA-G locus may shed some light into mechanisms underlying the regulation of HLA-G expression.