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.
Keywords: Carotid artery intima-media thickness, dyslipidemia, HIV lipodystrophy, insulin resistance,
metabolic syndrome, TNF-α single nucleotide polymorphism.
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