title: Cardiac morbidity in an HIV-1 lipodystrophy patient cohort expressing the TNF-α-238 G/A single nucleotide gene polymorphism.
abstract: In the current study we investigated the prevalence of the TNF-α 238G/A single nucleotide polymorphism (SNP) of the TNF-α gene in the development of lipodystrophy among HIV-1 infected individuals who had been receiving antiretroviral therapy (ART) in the immunodeficiency clinics of the National AIDS Research Institute (NARI) at Pune, India. We assessed the association of this SNP with the development of lipoatrophy/dyslipidemia and insulin resistance in these patients and measured carotid intima thickening which is a surrogate marker for chronic cardiac morbidity. Our results show that the incidence of the TNF-α 238G/A SNP is ~ two fold higher in patients with lipodystrophy as compared to those without lipodystrophy. Patients with lipodystrophy demonstrated a higher likelihood of the development of metabolic syndrome as evident by increased insulin sensitivity and increased percentage (%) β cell function. Further, a significant increase in left carotid intima thickness was observed in patients with lipodystrophy. Our study validates the association of the TNF-α 238G/A SNP allelic variant with the development of HIV- lipodystrophy via the modulation of TNF-α production, which contributes to dyslipidemia, increased lipolysis, increased insulin resistance, altered differentiation of adipocytes and increased carotid intima thickness. The contribution of genetic determinants such as the TNF-α 238G/A SNP to lipodystrophy, may provide insight into the mechanisms that underlie this disease condition and may be useful in the future for personalized therapy. Additionally, these findings will be useful in monitoring chronic cardiac morbidities among HIV infected individuals who express this SNP.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology & Rheumatology, State University of New York at Buffalo, 6074 UB's Clinical and Translational Research Center, 875 Ellicott St., Buffalo, NY 14203, USA. smahajan@buffalo.edu.
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Asmita
authors.initials: A
authors.lastname: Gaekwad
authors.forename: Jyoti
authors.initials: J
authors.lastname: Pawar
authors.forename: Srikanth
authors.initials: S
authors.lastname: Tripathy
authors.forename: Manisha
authors.initials: M
authors.lastname: Ghate
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharya
authors.forename: Hari Om
authors.initials: HO
authors.lastname: Singh
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
authors.forename: Ramesh
authors.initials: R
authors.lastname: Paranjape
authors.forename: Raman
authors.initials: R
authors.lastname: Gangakhedkar
mesh_terms: D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects; D059168:Carotid Intima-Media Thickness; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology; D050171:Dyslipidemias / Q000139:chemically induced / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D014409:Tumor Necrosis Factor-alpha