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Host determinants of HIV-1 control in African Americans.

ABSTRACT: We performed a whole-genome association study of human immunodeficiency virus type 1 (HIV-1) set point among a cohort of African Americans (n = 515), and an intronic single-nucleotide polymorphism (SNP) in the HLA-B gene showed one of the strongest associations. We use a subset of patients to demonstrate that this SNP reflects the effect of the HLA-B*5703 allele, which shows a genome-wide statistically significant association with viral load set point (P = 5.6 x 10(-10)). These analyses therefore confirm a member of the HLA-B*57 group of alleles as the most important common variant that influences viral load variation in African Americans, which is consistent with what has been observed for individuals of European ancestry, among whom the most important common variant is HLA-B*5701.

SUBMITTER: Pelak K

PROVIDER: S-EPMC2838940 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Host determinants of HIV-1 control in African Americans.

Pelak Kimberly K Goldstein David B DB Walley Nicole M NM Fellay Jacques J Ge Dongliang D Shianna Kevin V KV Gumbs Curtis C Gao Xiaojiang X Maia Jessica M JM Cronin Kenneth D KD Hussain Shehnaz K SK Carrington Mary M Michael Nelson L NL Weintrob Amy C AC

The Journal of infectious diseases 20100401 8

We performed a whole-genome association study of human immunodeficiency virus type 1 (HIV-1) set point among a cohort of African Americans (n = 515), and an intronic single-nucleotide polymorphism (SNP) in the HLA-B gene showed one of the strongest associations. We use a subset of patients to demonstrate that this SNP reflects the effect of the HLA-B*5703 allele, which shows a genome-wide statistically significant association with viral load set point (P = 5.6 x 10(-10)). These analyses therefor ...[more]

PMID: 20205591

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Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans.

Project description:A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; P= 3.4 × 10(-18)] and B*81:01 (OR = 4.8; P= 1.3 × 10(-9)). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P = 1.2 × 10(-21)) and explains the signal of several HLA-B alleles, including B*57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus P= 2.8 × 10(-15)) in the canonical F pocket, position 63 in the B pocket (P= 1.5 × 10(-3)) and the non-pocket position 245 (P= 8.8 × 10(-10)), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of HLA-B in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control.

| S-EPMC3441117 | biostudies-literature

Host genetics and HIV-1 viral load set-point in African-Americans.

Project description:OBJECTIVE:In a recent genome-wide association study of HIV-1-infected individuals in the Euro-CHAVI cohort, viral load set-point was strongly associated with genotypes defined by two single nucleotide polymorphisms (SNPs) (rs9264942 and rs2395029) within the human major histocompatibility complex (MHC) region on chromosome 6. We attempted to confirm this finding in African-Americans and to address whether these SNPs are in linkage disequilibrium with human leukocyte antigen (HLA) class I alleles that mediate innate and adaptive immunity. DESIGN:Our analyses relied on 121 African-American adolescents with chronic HIV-1 infection and quarterly immunological and virological outcome measures in the absence of therapy. METHODS:PCR-based techniques were used to genotype two SNPs along with HLA class I alleles. Their associations with HIV-1 viral load set-point and longitudinal CD4+ and CD8+CD38+ T cell counts were tested in univariate and multivariable models. RESULTS:The CC genotype at rs9264942 was associated with reduced viral load, but not with immunological outcomes or category of disease control. Consistent associations of favorable virologic outcomes were observed with B*57 (mostly B*5703) but not with rs2395029G allele at the HCP5 locus, which is in absolute linkage disequilibrium with B*5701 (in individuals of European descent), and not B*5703. CONCLUSION:Although rs9264942 and B*57 (but not rs2395029G) are clearly associated with control of viral load set-point among African-Americans, fine-mapping of MHC SNPs in populations of African and European descent should help reveal the causative variants and the underlying functional mechanisms.

| S-EPMC2663898 | biostudies-literature

IL28B genotype does not correlate with HIV control in African Americans.

Project description:BackgroundHIV-1 natural viral suppressors (NVS) are individuals that control HIV replication without antiretrovirals (also know as HIV elite controllers). We have recently shown that these individuals have an elevated rate of hepatitis C virus (HCV) clearance. Given the association of IL28B genotype, specifically the rs12979860 single nucleotide polymorphism (SNP) based CC genotype, with HCV clearance, we studied its association with HIV control in 172 African American HIV subjects and 173 race-matched controls.FindingsThe frequency of the CC genotype was 12.5% in the NVS, 14.7% in the LVL ("low viral load" cohort with 400-20,000 HIV-1 RNA copies/mL), 17.8% in the MHVL ("medium/high viral load" cohort with >20,000 HIV-1 RNA copies/mL), and 11.6% in an HIV-negative cohort. There was no statistical significance in the CC genotype distribution between these cohorts (p= 0.48 between the NVS and non-NVS HIV positive controls, p= 0.85 between NVS and HIV-negatives). We also did not observe any association between CC genotype distribution and HIV RNA viral load, as a continuous measure.ConclusionsThe IL28B CC genotype does not account for the noted HIV control in our specific NVS cohort. Further studies will be needed to determine if a common genetic factor can primarily account for any joint clearance of HCV and control of HIV.

| S-EPMC3170134 | biostudies-literature

Host genetic determinants of HIV infection

Project description:Broadly, the objectives of the study are to characterize genetic variation in any gene or genomic region in South African populations, in the first place HIV. The purpose is to apply this knowledge to establish assays and gene signatures to test in disease-association studies, and to study underlying mechanisms of disease causation/severity.

| EGAS00001005245 | EGA

Host transcriptome determinants for African Swine Fever (ASF)

Project description:In field studies and carefully controlled artificial infections, there is host variation in response to ASF infections. To better understand the mechanisms underlying this diversity and distinguish between resilient and susceptible pigs to African Swine Fever (ASF), the differentially expressed genes (DEGs) were studied between the recovered versus non-recovered pigs before and after an infection challenge and also among non-recovered animals over time. In total, 17 Babraham pigs were sampled. Twelve animals were randomly immunized with low virulent ASFV isolate, and the others received the sham vaccine. All animals were then challenged with the virulent ASFV isolate 18 days after the immunization. Except for five animals, all showed clinical signs and dead between 4 and 6 days later. RNA sequencing was done for whole blood samples collected pre-infection, one day, and one week post-infection.

2023-02-17 | E-MTAB-12608 | biostudies-arrayexpress

HIV-infected African Americans are willing to participate in HIV treatment trials.

Project description:Despite the high prevalence rates of HIV infection in the African-American community, African Americans remain underrepresented in HIV treatment trials.(1) To develop a questionnaire that measures attitudes and concerns about HIV treatment trials among HIV-infected African Americans at a university-based clinic. (2) To determine actual participation rates and willingness to participate in future HIV treatment trials among HIV-infected African Americans at a university-based clinic.Questionnaire development and cross-sectional survey.In a sample of 200 HIV-infected African-American adults receiving medical care at the Pittsburgh AIDS Center for Treatment (a university-based ambulatory clinic), we assessed research participation rates and willingness to participate in future HIV treatment trials, trust in the medical profession, sociodemographic characteristics, attitudes, and concerns about HIV treatment trials.Research participation rates and willingness to participate in future HIV treatment trials.Only 57% of survey respondents had ever been asked to participate in an HIV treatment trial but 86% of those asked said yes. Prior research participation was significantly related to willingness to participate in future HIV treatment trials (P = .001). Contrary to previous studies, neither trust/distrust in the medical profession nor beliefs about the dishonesty of researchers was associated with research participation rates or willingness to participate in future HIV treatment trials.Having never been asked to participate in research is a major barrier to the participation of HIV-infected African Americans in HIV treatment trials. African Americans who seek medical care for HIV infection should be asked to participate in HIV treatment trials.

| S-EPMC1824784 | biostudies-other

Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans.

Project description:OBJECTIVE:The etiology of knee osteoarthritis (OA), the most common form of arthritis, is complex and may differ by race or ethnicity. In recent years, genetic studies have identified many genetic variants associated with OA, but nearly all the studies were conducted in European whites and Asian Americans. Few studies have focused on the genetics of knee OA in African Americans. METHODS:We performed a genome-wide association study of radiographic knee OA in 1217 African Americans from 2 North American cohort studies: 590 subjects from the Johnston County Osteoarthritis Project and 627 subjects from the Osteoarthritis Initiative. Analyses were conducted in each cohort separately and combined in an inverse variance fixed effects metaanalysis, which were then included in pathway analyses. We additionally tested 12 single-nucleotide polymorphisms robustly associated with OA in European white populations for association in African Americans. RESULTS:We identified a genome-wide significant variant in LINC01006 (minor allele frequency 12%; p = 4.11 × 10-9) that is less common in European white populations (minor allele frequency < 3%). Five other independent loci reached suggestive significance (p < 1 × 10-6). In pathway analyses, dorsal/ventral neural tube patterning and iron ion transport pathways were significantly associated with knee OA in African Americans (false discovery rate < 0.05). We found no evidence that previously reported OA susceptibility variants in European whites were associated with knee OA in African Americans. CONCLUSION:These results highlight differences in the genetic architecture of knee OA between African American and European whites. This finding underscores the need to include more diverse populations in OA genetics studies.

| S-EPMC5668168 | biostudies-literature

Genetic determinants influencing human serum metabolome among African Americans.

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Myeloma in African Americans: Myeloma gDNA vs. Control gDNA

Project description:Epidemiological data have suggested that African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as compared to European Americans (EA). Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from three studies and EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs. 52%; p=0.032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based upon gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients.

2013-02-25 | GSE44271 | GEO

Host transcriptome determinants for African Swine Fever (ASF)

Project description: Not available

| S-BSST970 | biostudies-other