miércoles, 29 de diciembre de 2010
AIDS. 2010 Dec 14. [Epub ahead of print]
Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.
Petrovski S, Fellay J, Shianna KV, Carpenetti N, Kumwenda J, Kamanga G, Kamwendo DD, Letvin NL, McMichael AJ, Haynes BF, Cohen MS, Goldstein DB; on behalf of the Center for HIV/AIDS Vaccine Immunology (CHAVI).
aCenter for Human Genome Variation, School of Medicine, Duke University, Durham, North Carolina, United States of America bCollege of Medicine, University of Malawi, Blantyre, Malawi cUniversity of North Carolina Project, Lilongwe, Malawi dDivision of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America eMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom fDuke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America gDepartment of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA. *These authors contributed equally to this work.
To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. Here we perform a genome-wide association study (GWAS) in a population of 1,532 individuals from Malawi, a country with high prevalence of HIV-1 infection, to investigate whether common genetic variants associate with HIV-1 susceptibility in Africans. Using single nucleotide polymorphisms (SNPs) present on the genome-wide chip, we also investigated previously reported associations with HIV-1 susceptibility or acquisition. Recruitment was coordinated by the Center for HIV/AIDS Vaccine Immunology at two sexually transmitted infection clinics. HIV status was determined by HIV rapid tests and nucleic acid testing.After quality control, the population consisted of 848 high-risk seronegative and 531 HIV-1 seropositive individuals. Logistic regression testing in an additive genetic model was performed for SNPs that passed quality control. No single SNP yielded a significant P-value after correction for multiple testing. The study was sufficiently powered to detect markers with genotype relative risk ≥ 2.0 and minor allele frequencies ≥12%. This is the first GWAS of host determinants of HIV-1 susceptibility, performed in an African population. The absence of any significant association can have many possible explanations: rarer genetic variants or common variants with weaker effect could be responsible for the resistance phenotype; alternatively, resistance to HIV-1 infection might be due to non-genetic parameters or to complex interactions between genes, immunity and environment.
PMID: 21160409 [PubMed - as supplied by publisher]
Common human genetic variants and HIV-1 susceptibi... [AIDS. 2010] - PubMed result