Reappraisal of the relationship between the HIV-1-protective single-nucleotide polymorphism 35 kilobases upstream of the HLA-C gene and surface HLA-C expression.
Ontology highlight
ABSTRACT:
SUBMITTER: Corrah TW
PROVIDER: S-EPMC3067890 | biostudies-literature | 2011 Apr
REPOSITORIES: biostudies-literature
Publications
Reappraisal of the relationship between the HIV-1-protective single-nucleotide polymorphism 35 kilobases upstream of the HLA-C gene and surface HLA-C expression.
Corrah Tumena W TW Goonetilleke Nilu N Kopycinski Jakub J Deeks Steven G SG Cohen Myron S MS Borrow Persephone P McMichael Andrew A Brackenridge Simon S
Journal of virology 20110119 7
Previous studies have found an association between a single-nucleotide polymorphism 35 kb upstream of the HLA-C locus (-35 SNP), HLA-C expression, and HIV-1 set point viral loads. We show that the difference in HLA-C expression across -35 SNP genotypes can be attributed primarily to the very low expression of a single allelic product, HLA-Cw7, which is a common HLA type. We suggest that association of the -35 SNP and HIV-1 load manifests as a result of linkage disequilibrium of this polymorphism ...[more]
Similar Datasets
Project description:INTRODUCTION:The SNP HLA-C-35 kb (rs9264942) may contribute to the host immune defense mechanism by affecting the cell surface expression pattern of HLA-C and antigen presentation to CD8+ cytotoxic cells. Thus, this SNP may contribute to intracellular multidrug-resistant (MDR)-tuberculosis (TB) infection. AIM:To examine the association between the SNP HLA-C-35 kb (rs9264942) and the clinical profile of MDR-TB infection. SETTINGS AND DESIGN:MDR-TB-positive patients were followed from May 2012 to December 2013 to observe the progression of MDR-TB infection. Non-TB individuals and non-MDR-TB individuals were also recruited as controls. MATERIALS AND METHODS:The patients' HLA-C-35 kb (rs9264942) status was determined by PCR. RESULTS:The C allele was slightly more frequent in the MDR-TB patients than in the non-MDR TB patients (OR= 1.28; 95% CI: 0.701 - 2.328). The C allele was found to be more frequent in the MDR-TB patients exhibiting pulmonary fibrosis (OR= 2.13; 95% CI: 0.606 - 7.480) or pulmonary infiltrates (OR= 3.17; 95% CI: 0.690 - 14.598) and among the MDR-TB patients who were classified as underweight (OR= 8.00; 95% CI: 1.261 - 50.770). The CC genotype was associated with the treatment after failure of category II group (OR= 4.17; 95% CI: 1.301 - 13.346). CONCLUSION:The C allele SNP HLA-C-35 kb (rs9264942) may contribute to the clinical profile in MDR-TB infection.
| S-EPMC4606233 | biostudies-literature
Project description:Aim of the studyAssociation of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir.Methods414 HIV-positive Caucasians (30% women) aged 19-73 years were genotyped for HLA-C -35 (rs9264942) and HLA-B*5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes.ResultsHLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B*5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002) compared to T/T group [mean:4.66 log (SD:1.03) vs. 5.07 (SD:0.85) log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537) cells/?l vs. median: 203 (IQR:55-410) cells/?l, respectively] (p=0.0007). Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/?l] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/?l] (p=0.006). Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/?l, p=0.04, respectively) compared to HLA-B*5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3]) HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682) vs. median: 361 (IQR: 205-574) cells/?l, respectively) were found in individuals with HLA-B*5701(+)/HLA-C -35 C/C haplotype.ConclusionsHLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count) and virologic (lower pretreatment HIV viral load) variables. This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.
| S-EPMC4465896 | biostudies-literature
Project description:BACKGROUND:Human leukocyte antigen (HLA)-DP is an HLA class II molecule. Overexpression of HLA class II molecules in placental trophoblast cells may induce pregnancy loss. However, the association between HLA-DP and pregnancy loss remains unclear. HLA-DPA1 is an HLA-DP peptide chain. The objective of this study was to assess the association between HLA-DPA1 genetic polymorphism and anembryonic pregnancy, a type of early pregnancy loss, in the Chinese population. METHODS:A case-control study was designed to compare the frequencies of HLA-DPA1 gene polymorphisms in an anembryonic pregnancy group and a control group. Sixty-eight cases and 122 controls were recruited. Statistical analysis was performed to assess the correlation between single-nucleotide polymorphisms (SNPs) and anembryonic pregnancy susceptibility. MassARRAY high-throughput DNA analysis was used to analyze 19 HLA-DPA1 SNPs. To explore how HLA-DPA1 polymorphism could affect anembryonic pregnancy, HLA-DPA1 serum levels were analyzed by ELISA. RESULTS:Homozygous typing of rs1431403 (CC and TT) significantly increased the risk of anembryonic pregnancy in the case group (ORCC = 3.13, 95% CI: 1.50-6.53; ORTT = 2.96, 95% CI: 1.31-6.66; ORCC+TT = 3.06, 95% CI: 1.62-5.78). In samples with high HLA-DPA1 levels (?1,500 pg/ml), the homozygous rs1431403 genotypes (nCC = 21, 43.8%; nTT = 20, 57.1%) were observed more frequently than were heterozygous genotypes. CONCLUSION:HLA-DPA1 rs1431403 may be a risk factor for anembryonic pregnancy in the Chinese population. Homozygous rs1431403 genotypes (CC and TT) may increase the risk of anembryonic pregnancy by aberrantly increasing the HLA-DPA1 levels.
| S-EPMC6978238 | biostudies-literature
Project description:A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.
| S-EPMC2887091 | biostudies-literature
Project description:Background:Preeclampsia is a condition associated with systemic disorders in the mother and the fetus. However, the exact causes of preeclampsia are unknown, but several genetics and environmental factors play role in development of this disease. Major histocompatibility complex role is very important during pregnancy through which the fetus is not rejected by mother's immune system. Objective:In this study, we investigated the relationship of the human leukocyte antigen (HLA)-DQA1*0102/HLA-DQB1*0602 polymorphism with preeclampsia. Materials and Methods:Genomic DNA of 181 pregnant women with a history of preeclampsia as the case group and 228 pregnant women with no history of preeclampsia as the controls were extracted. The HLA-DQA1*0102/HLA-DQB1*0602 polymorphisms of all DNA samples were identified by the SSP-PCR method. Frequencies difference of variables between case and control groups were calculated by Chi-square test. The ethnic origin of the participants in this study was extracted from their medical records. Results:There was a significant association between preeclampsia and Sistani ethnic group (p=0.031). Moreover, there was a significant association between preeclampsia and frequencies of allele HLA-DQB1*0602 (p<0.001), and genotypes of heterozygote (+0102/-0602) (p<0.001) and negative homozygote (-0102/-0602) (p=0.005). There also was an association between allele HLA-DQB1*0602 and preeclampsia in Fars ethnic group (p=0.028). Conclusion:It seems that immune incompatibility may have an important role in preeclampsia predisposition. According to our results, the lack of locus HLA-DQB1*0602 may be a risk factor for preeclampsia.
| S-EPMC5893932 | biostudies-literature
Project description:Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB). The association between HBV infection and human leukocyte antigen- (HLA-) DQ polymorphism (rs2856718 and rs7453920) has been demonstrated in other studies; however, the results were controversial or inconclusive. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association between HLA-DQ polymorphism (rs2856718 and rs7453920) and HBV infection risk. A total of 11 articles were used to evaluate the effect of the two polymorphisms on risk of HBV infection. The pooled data showed that HLA-DQ rs2856718-G polymorphism showed protection against HBV infection, and rs2856718-A was a risk factor for chronic HBV infection. The pooled risk estimates indicated that HLA-DQ rs7453920-A polymorphism was associated with decreased risk of HBV infection, and rs7453920-G serves as a risk factor in HBV infection. However, these stratified analyses were lacking credibility due to the limitation of correlational study numbers; further investigation on a large population and different ethnicities is warranted.
| S-EPMC5420426 | biostudies-literature
Project description:Understanding the mechanisms by which some individuals are able to naturally control HIV-1 infection is an important goal of AIDS research. We here describe the case of an HIV-1(+) woman, CASE1, who has spontaneously controlled her viremia for the last 14 of her 20 years of infection.CASE1 has been clinically monitored since 1993. Detailed immunological, virological and histological analyses were performed on samples obtained between 2009 and 2011.As for other Elite Controllers, CASE1 is characterized by low to undetectable levels of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC) associated HIV-1 DNA and reduced in vitro susceptibility of target cells to HIV-1 infection. Furthermore, a slow rate of virus evolution was demonstrated in spite the lack of assumption of any antiretroviral agent. CASE1 failed to transmit HIV-1 to either her sexual male partner or to her child born by vaginal delivery. Normal values and ratios of T and B cells were observed, along with normal histology of the intestinal mucosa. Attempts to isolate HIV-1 from her PBMC and gut-derived cells were unsuccessful, despite expression of normal cell surface levels of CD4, CCRC5 and CXCR4. CASE1 did not produce detectable anti-HIV neutralizing antibodies in her serum or genital mucosal fluid although she displayed potent T cell responses against HIV-1 Gag and Nef. CASE1 also possessed multiple genetic polymorphisms, including HLA alleles (B*14, B*57, C*06 and C*08.02) and HLA-C single nucleotide polymorphisms (SNPs, rs9264942 C/C and rs67384697 del/del), that have been previously individually associated with spontaneous control of plasma viremia, maintenance of high CD4(+) T cell counts and delayed disease progression.CASE1 has controlled her HIV-1 viremia below the limit of detection in the absence of antiretroviral therapy for more than 14 years and has not shown any sign of immunologic deterioration or disease progression. Co-expression of multiple protective HLA alleles, HLA-C SNPs and strong T cell responses against HIV-1 proteins are the most likely explanation of this very benign case of spontaneous control of HIV-1 disease progression.
| S-EPMC4272524 | biostudies-literature
Project description:Regulation of NK cell activity is mediated through killer-cell immunoglobulin-like receptors (KIR) ability to recognize human leukocyte antigen (HLA) class I molecules as ligands. Interaction of KIR and HLA is implicated in viral infections, autoimmunity, and reproduction and there is growing evidence of the coevolution of these two independently segregating gene families. By leveraging KIR and HLA-C data from 1000 Genomes consortium we observed that the KIR2DL1 variant rs2304224 * T is associated with lower expression of HLA-C in individuals carrying the ligand HLA-C2 (p = 0.0059). Using flow cytometry, we demonstrated that this variant is also associated with higher expression of KIR2DL1 on the NK cell surface (p = 0.0002). Next, we applied next generation sequencing to analyze KIR2DL1 sequence variation in 109 Euro and 75 Japanese descendants. Analyzing the extended haplotype homozygosity, we show signals of positive selection for rs4806553 * G and rs687000 * G, which are in linkage disequilibrium with rs2304224 * T. Our results suggest that lower expression of HLA-C2 ligands might be compensated for higher expression of the receptor KIR2DL1 and bring new insights into the coevolution of KIR and HLA.
| S-EPMC7478174 | biostudies-literature
Project description:Diarrheal disease (DD) due to contaminated water is a major cause of child mortality globally. Forests and wetlands can provide ecosystem services that help maintain water quality. To understand the connections between land cover and childhood DD, we compiled a database of 293,362 children in 35 countries with information on health, socioeconomic factors, climate, and watershed condition. Using hierarchical models, here we find that higher upstream tree cover is associated with lower probability of DD downstream. This effect is significant for rural households but not for urban households, suggesting differing dependence on watershed conditions. In rural areas, the effect of a 30% increase in upstream tree cover is similar to the effect of improved sanitation, but smaller than the effect of improved water source, wealth or education. We conclude that maintaining natural capital within watersheds can be an important public health investment, especially for populations with low levels of built capital.Globally diarrheal disease through contaminated water sources is a major cause of child mortality. Here, the authors compile a database of 293,362 children in 35 countries and find that upstream tree cover is linked to a lower probability of diarrheal disease and that increasing tree cover may lower mortality.
| S-EPMC5634511 | biostudies-literature
Project description:Prostate cancer (PCa) has almost the highest genetic transmission that mimics an autosomal dominance hereditary pattern of cancers in some families. Its incidence in Arab countries was reported to be steadily increasing. Aim. To determine the relevance of HLA-DPA1 rs3077 (A/G) SNP with prostate cancer's risk and/or severity. Subjects and Methods. Forty PCa patients and forty age matched patients with benign prostatic hyperplasia (BPH), as a control group, were enrolled in the study. Serum levels of urea, creatinine, total prostate-specific antigen (PSA), and free PSA were measured. PSA ratio was determined as well. Genotyping of HLA-DPA1 rs3077 (A/G) SNP was done using real-time PCR. Results. The measured lab parameters, except free PSA, were significantly higher among PCa patients in comparison to controls (P < 0.001 ∗ ). Moreover, PSA ratio was significantly high among PCa patients (P < 0.001 ∗ ). HLA-DPA1 rs3077 GG genotype was more frequent in PCa patients and the associated OR was 2.546 (P=0.059), while AA genotype was more frequent in the control group and the associated OR was 0.145 (P=0.081). Frequency of G allele was higher among PCa patients than the control group while A allele frequency was significantly decreased (P=0.034 ∗ ) (protective allele). On multivariate analysis, there is no significant correlation found between HLA-DPA1 rs3077 SNP and PSA ratio (OR = 4.5, 95% CI = 1.2-17.4, P=0.856). Conclusion. HLA-DPA1 rs3077 G allele could be a risk factor for prostate cancer. However, HLA-DPA1 rs3077 SNP has no relation to PCa severity.
| S-EPMC8084672 | biostudies-literature