Variants in host viral replication cycle genes are associated with heterosexual HIV-1 acquisition in Africans

J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):127-34. doi: 10.1097/QAI.0000000000000113.

Abstract

Objective: We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.

Methods: Using a nested case-control study within a cohort of heterosexual HIV-1-serodiscordant couples, we genotyped 475 haplotype-tagging single-nucleotide polymorphisms (tagSNPs) and 18 SNPs previously associated with HIV-1 transmission and/or progression (candidate SNPs) in 51 host genes. We used logistic and Cox proportional hazard regression with adjustment for sex, age, and population stratification to detect SNP associations with HIV-1 acquisition, plasma HIV-1 set point, and a composite measure of HIV-1 disease progression. Significant thresholds for tagSNP, but not candidate SNP, associations were subjected to Bonferroni correction for multiple testing.

Results: We evaluated 491 HIV-1-infected and 335 HIV-1-uninfected individuals for 493 SNPs, 459 of which passed quality control filters. Candidate SNP PPIA rs8177826 and tagSNP SMARCB1 rs6003904 were significantly associated with HIV-1 acquisition risk (odds ratio = 0.14, P = 0.03, and odds ratio = 2.11, Pcorr = 0.01, respectively). Furthermore, the TT genotype for CCR5 rs1799988 was associated with a mean 0.2 log10 copies per milliliter lower plasma HIV-1 RNA set point (P = 0.04). We also identified significant associations with HIV-1 disease progression for variants in FUT2 and MBL2.

Conclusions: Using a targeted gene approach, we identified variants in host genes whose protein products interact with HIV-1 during the virus replication cycle and were associated with HIV-1 outcomes in this African cohort.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Continental Ancestry Group*
  • Case-Control Studies
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • HIV Infections / epidemiology*
  • HIV Infections / genetics*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Haplotypes
  • Humans
  • Logistic Models
  • Male
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • RNA, Viral / blood
  • Viral Load
  • Virus Replication*
  • Young Adult

Substances

  • RNA, Viral