CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from Guinea-Bissau, West Africa.

Hennig BJ, Velez-Edwards DR, Schim van der Loeff MF, Bisseye C, Edwards TL, Tacconelli A, Novelli G, Aaby P, Kaye S, Scott WK, Jaye A, Whittle HC, Williams SM, Hill AV, Sirugo G
J Acquir Immune Defic Syndr. 2011 56 (1): 1-8

PMID: 20924289 · DOI:10.1097/QAI.0b013e3181f638ed

OBJECTIVES - The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209.

DESIGN - This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau.

METHODS - We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4 T-cell count (high vs. low).

RESULTS - The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004).

CONCLUSIONS - Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility.

MeSH Terms (23)

Adult AIDS Serodiagnosis CD4 Antigens CD4 Lymphocyte Count Cell Adhesion Molecules Disease Progression Female Genotype Guinea-Bissau Haplotypes HIV-1 HIV-2 HIV Infections Humans Lectins, C-Type Linkage Disequilibrium Logistic Models Male Middle Aged Polymerase Chain Reaction Polymorphism, Single Nucleotide Receptors, Cell Surface Viral Load

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