Exploration of associations between phospholipase A2 gene family polymorphisms and AIDS progression using the SNPleX (TM) method

Members of the secreted phospholipase A2 (PLA2) protein family can inhibit HIV-1 virus replication in vitro. To evaluate the impact of PLA2 gene polymorphisms on AIDS disease development, we studied 12 family members using SNPlex (TM) technology that permitted simultaneous typing of 70 tagging Single Nucleotide Polymorphisms (tagSNPs). The study utilized HIV-1 seropositive donors, with slow progressor (n = 168) or rapid progressor (n = 54) status, plus 355 control subjects. All donors were Caucasian (total 577 individuals). Genetic associations yielded mainly 0.01 < p < 0.05, but lower p-values were obtained for four tagSNPs and seven haplotype alleles. These stronger associations corresponded to both secreted (PLA2G2A, PLA2G2D and PLA2G3) and cytosolic (PLA2G4A and PLA2G6) PLA2 genes, including three (PLA2G2A, PLA2G2D and PLA2G4A) implicated in the pathogenesis of other diseases. Our results suggest that the PLA2 gene family may represent genes of interest for a larger study targeting all the known tagSNPs in the PLA2 genes. The data presented in this study will have to be confirmed in other AIDS cohorts and will also be useful for studies undertaken on the PLA2 gene family in other disease cohorts. (c) 2007 Elsevier Masson SAS. All rights reserved.