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

  • Petrovski S
  • Fellay J
  • Shianna K
 et al. 
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Abstract

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. © 2011 Wolters Kluwer Health , Lippincott Williams & Wilkins.

Author-supplied keywords

  • Africa
  • HIV-1
  • acquisition
  • genome-wide association study
  • resistance

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Authors

  • Slavé Petrovski

  • Jacques Fellay

  • Kevin V. Shianna

  • Nicole Carpenetti

  • Johnstone Kumwenda

  • Gift Kamanga

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