P065Polymorphisms in pro- and anti-inflammatory cytokine genes and HIV infection in North Indians

Abstract

Aim Various candidate gene based studies on available specialized cohorts viz. viremic controllers, elite controllers, exposed uninfected individuals, rapid and slow progressor individuals support role of immunogenetic factors in defining HIV/AIDS outcome. In this context, the differential genetic influence of cytokine genes on immune response network can affect the establishment and spread of HIV infection; however information is limited on Indian populations. Therefore, here we aimed to explore the largely unknown genetic influence of various pro (IL-1, IL-2, IFN-γ etc.) and anti inflammatory (IL-4, IL-10, TGF-β etc.) cytokine gene polymorphisms on HIV infection, particularly in North Indian population. Methods We enrolled a total of 157 HIV patients, 130 healthy and 27 exposed uninfected healthy controls from the North Indian states after obtaining the institutional ethical approval and participants’ informed consent. Evaluation of 22 functionally relevant single nucleotide polymorphisms in 13 cytokine and their receptor genes was performed by genotyping using PCR-SSP based approach. Appropriate softwares and statistical tests were used (chi square and Fishers Exact test wherever applicable) for comparison. Results Frequencies of most of the analyzed variants were statistically indifferent between HIV patients and uninfected healthy controls at the allelic, genotypic and haplotypic levels. Significantly higher allelic frequencies of IL-1α -889 T and IL-4 -1098 T were observed in HIV patients, while IL-1α -889 CC, IL-4 -1098 GG and IL-6 nt565 AA genotypes were observed significantly lower as compared healthy uninfected controls. Conclusions This study represents the first report that highlights the influence of various cytokine gene polymorphisms in context of HIV infection in the North Indians. The observed associated variants are known to have functional relevance towards modulating the inflammatory mileu.