Dataset Information

Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.

ABSTRACT: OBJECTIVE:The bone marrow stromal cell antigen 2 (BST2) gene encodes a host restriction factor that acts as an innate immune sensor of HIV-1 exposure and suppresses release of HIV-1 particles. We aimed to identify associations of variants in the BST2 gene region with HIV-1 acquisition and disease progression. DESIGN/METHODS:Using HIV+ cases and HIV- controls from the Urban Health Study (n=3136 African Americans and European Americans who inject drugs), we tested 470 variants in BST2 and its flanking regions for association with HIV-1 acquisition and log-transformed viral load. RESULTS:We found that the single nucleotide polymorphism (SNP) rs113189798 surpassed the P value threshold corrected for multiple testing. The rs113189798-G allele (frequency=16% in African Americans, 4% in European Americans) was associated with increased HIV-1 acquisition risk (meta-analysis P=1.43?×?10): odds ratio (95% confidence interval) of 1.22 (1.01-1.49) in African Americans and 2.17 (1.43-3.33) in European Americans. We also found that the previously reported rs12609479-A allele (frequency=35% in African Americans, 81% in European Americans) was nominally associated with decreased risk of acquiring HIV-1 in our study (meta-analysis P=0.036). Rs12609479-A is predicted to increase BST2 expression and thereby decrease risk of acquiring HIV-1. Rs113189798 and rs12609479 were only weakly correlated [square of the correlation coefficient (r)=0.2-0.4] and represented distinct association signals. None of our tested variants were significantly associated with log-transformed viral load among the HIV-infected cases. CONCLUSION:Our findings support BST2 as a genetic susceptibility factor for HIV-1 acquisition: identifying a novel SNP association for rs13189798 and linking the previously reported regulatory SNP rs12609479 to HIV-1 acquisition.

SUBMITTER: Hancock DB

PROVIDER: S-EPMC4439198 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.

Hancock Dana B DB Gaddis Nathan C NC Levy Joshua L JL Bierut Laura J LJ Kral Alex H AH Johnson Eric O EO

AIDS (London, England) 20150401 7

<h4>Objective</h4>The bone marrow stromal cell antigen 2 (BST2) gene encodes a host restriction factor that acts as an innate immune sensor of HIV-1 exposure and suppresses release of HIV-1 particles. We aimed to identify associations of variants in the BST2 gene region with HIV-1 acquisition and disease progression.<h4>Design/methods</h4>Using HIV+ cases and HIV- controls from the Urban Health Study (n=3136 African Americans and European Americans who inject drugs), we tested 470 variants in BS ...[more]

PMID: 25985399

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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.

Dataset Information

Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.

Publications

Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs.

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