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Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.

Publication ,  Journal Article
Petrovski, S; Fellay, J; Shianna, KV; Carpenetti, N; Kumwenda, J; Kamanga, G; Kamwendo, DD; Letvin, NL; McMichael, AJ; Haynes, BF; Cohen, MS ...
Published in: AIDS
February 20, 2011

OBJECTIVE: 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. We investigated whether common genetic variants associate with HIV-1 susceptibility in Africans. METHODS: We performed a genome-wide association study (GWAS) in a population of 1532 individuals from Malawi, a country with high prevalence of HIV-1 infection. 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. RESULTS: 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 or more and minor allele frequencies 12% or more. CONCLUSION: 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 nongenetic parameters or to complex interactions between genes, immunity and environment.

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Published In

AIDS

DOI

EISSN

1473-5571

Publication Date

February 20, 2011

Volume

25

Issue

4

Start / End Page

513 / 518

Location

England

Related Subject Headings

  • Young Adult
  • Virology
  • Receptors, CCR5
  • Phenotype
  • Middle Aged
  • Male
  • Malawi
  • Humans
  • HIV-1
  • HIV Infections
 

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Petrovski, S., Fellay, J., Shianna, K. V., Carpenetti, N., Kumwenda, J., Kamanga, G., … Center for HIV/AIDS Vaccine Immunology, . (2011). Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. AIDS, 25(4), 513–518. https://doi.org/10.1097/QAD.0b013e328343817b
Petrovski, Slavé, Jacques Fellay, Kevin V. Shianna, Nicole Carpenetti, Johnstone Kumwenda, Gift Kamanga, Deborah D. Kamwendo, et al. “Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.AIDS 25, no. 4 (February 20, 2011): 513–18. https://doi.org/10.1097/QAD.0b013e328343817b.
Petrovski S, Fellay J, Shianna KV, Carpenetti N, Kumwenda J, Kamanga G, et al. Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. AIDS. 2011 Feb 20;25(4):513–8.
Petrovski, Slavé, et al. “Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.AIDS, vol. 25, no. 4, Feb. 2011, pp. 513–18. Pubmed, doi:10.1097/QAD.0b013e328343817b.
Petrovski S, Fellay J, Shianna KV, Carpenetti N, Kumwenda J, Kamanga G, Kamwendo DD, Letvin NL, McMichael AJ, Haynes BF, Cohen MS, Goldstein DB, Center for HIV/AIDS Vaccine Immunology. Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. AIDS. 2011 Feb 20;25(4):513–518.

Published In

AIDS

DOI

EISSN

1473-5571

Publication Date

February 20, 2011

Volume

25

Issue

4

Start / End Page

513 / 518

Location

England

Related Subject Headings

  • Young Adult
  • Virology
  • Receptors, CCR5
  • Phenotype
  • Middle Aged
  • Male
  • Malawi
  • Humans
  • HIV-1
  • HIV Infections