title: Combination of low producer AA-genotypes in IFN-γ and IL-10 genes makes a high risk genetic variant for HIV disease progression.
abstract: Rate of HIV disease progression varies considerably among individuals, host genetic makeup be one of the possible reasons. We aimed to determine association of functional single nucleotide polymorphism (SNPs), (-179G/T and +874T/A) in IFN-γ and (-1082A/G, -819C/T and -592C/A) in IL-10 genes, with the rate of disease progression or susceptibility to HIV infection. Therapy naïve HIV infected individuals from North India, categorized as slow progressors or fast progressors and HIV exposed seronegative individuals were recruited for this study. Genotyping results revealed significantly higher frequencies of low producer AA genotype at +874T/A in IFN-γ gene and -592C/A position in IL-10 gene in FPs (p<0.002). Multifactor dimensional reduction (MDR) analysis revealed this to be a high risk combination for faster disease progression in HIV-1 infected individuals. Low producer AA genotype carriers at +874T/A in IFN-γ gene produced significantly low amounts of cellular IFN-γ. Low producing haplotype 'ATA' at -1082, -819 and -592 loci in IL-10 gene was significantly over-represented in FPs as compared to SPs (p<0.01) and these individuals showed poor response to therapy in terms of CD4 count gains after one year of ART, compared to high producing haplotype (GCC) carriers. Thus, a combination of genetic variations in IFN-γ and IL-10 cytokine genes in a single host associate with HIV disease progression and may help clinicians to better manage the HIV disease if known earlier.
authors.affiliation: Departments of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Sukhvinder
authors.initials: S
authors.lastname: Singh
authors.affiliation: Departments of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Aman
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Departments of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. Electronic address: arora.sunil@pgimer.edu.in.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Arora
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Disease progression; HIV-1; IFN-γ; IL-10; North-India; SNPs