title: Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism with susceptibility to HIV-1 infection in North Indians.
abstract: The clinical course and outcome of HIV-1 infection are highly variable among individuals. Interleukin 4 (IL-4) is a key T helper 2 cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, downregulation of CCR5 and upregulation of CXCR4, the main co-receptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 promoter 589 C/T and IL-4 Ralpha I50V affect the susceptibility to HIV infection and its progression to AIDS in North Indian individuals. The study population consisted of 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, III), 50 HIV-1 exposed seronegative (HES), and 305 HIV-1 seronegative (HSN) individuals. The subjects were genotyped for IL-4 589 C/T promoter polymorphism and IL-4 Ralpha I50V by polymerase chain reaction restriction fragment length polymorphism. The results showed that IL-4 589 C/T was not associated with the risk of HIV infection and disease progression. However, the IL-4Ralpha I50 allele and genotype was significantly increased in HSP compared to HSN and HSP and was associated with risk of HIV infection. The frequency of IL-4Ralpha I50 allele in the HSP group was higher than in HSN (76.11 vs. 64.75%; P = 0.000; OR = 1.734) and HES (76.11% vs. 62.00%; P = 0.007; OR = 1.953). Homozygous IL-4Ralpha I50I genotype was significantly increased in HSP group compared with HSN (58.88% vs. 44.26%; P = 0.002; OR = 1.804) and HES (58.88% vs. 42.00%; P = 0.038; OR = 1.978). The present study for the first time suggests an association of IL-4Ralpha I50 allele with increased likelihood of HIV-1 infection in North Indian population. Further studies are required to confirm these findings and understand the effect of IL-4Ralpha polymorphism on the outcome of HIV-1 infection.
authors.affiliation: Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Animesh
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Anurag
authors.initials: A
authors.lastname: Rathore
authors.forename: Tapan N
authors.initials: TN
authors.lastname: Dhole
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D007194:India; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D019948:Receptors, Interleukin-4; D015847:Interleukin-4