Investigation of SIRT1 gene variants in HIV-associated lipodystrophy and metabolic syndrome.

Carmela Farias Da Silva Tagliari,Vanessa Suñé Mattevi,Cáren Nunes De Oliveira,Patrícia Baptista Da Silva,Eduardo Sprinz,Rosmeri Kuhmmer Lazzaretti,Regina Kuhmmer Notti,Rafael Linden,Greice Meyer Vogel

doi:10.1590/1678-4685-gmb-2019-0142

Abstract

HIV-infected individuals on chronic use of highly active antiretroviral therapy (HAART) are more likely to develop adipose tissue and metabolic disorders, such as lipodystrophy (LD) and metabolic syndrome (MetS). The development of these phenotypes is known to be multifactorial. Thus, variants in genes implicated in adipogenesis and lipid metabolism may increase susceptibility to LD and MetS. Sirtuin 1 (SIRT1) may influence the outcome of these disturbances due to its role in the regulation of transcription factors involved in energy regulation. Therefore, we genotyped four polymorphisms located in SIRT1 (rs2273773 T>C, rs12413112 G>A, rs7895833 A>G, rs12049646 T>C) in 832 HIV-infected patients receiving HAART by real-time polymerase chain reaction. The prevalence of LD was 55.8% and MetS was 35.3%. Lipoatrophy was the most prevalent subtype in all samples (38.0%) and showed significant difference between white and non-white individuals (P = 0.002). None of the genetic variants investigated in SIRT1 was associated with LD and MetS. White individuals and those in longer time of HAART use were more likely to develop LD. We concluded that these SIRT1 polymorphisms are not predictive factors to the development of lipodystrophy and metabolic syndrome in HIV-infected individuals from Brazil.

Highlights

The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is globally recognized as an epidemiological phenomenon
It has been shown that HIV-infected individuals in regular use of Highly active antiretroviral therapy (HAART) are at increased risk of developing a variety of metabolic disorders and fat redistribution
The latter is known as lipodystrophy syndrome (LD) and can be present as the following subtypes: lipoatrophy (LA), which consists of peripheral subcutaneous fat loss; lipohypertrophy (LH), when there is adipose tissue accumulation, mainly central fat gain

Summary

Introduction

The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is globally recognized as an epidemiological phenomenon. It has been shown that HIV-infected individuals in regular use of HAART are at increased risk of developing a variety of metabolic disorders and fat redistribution (Cunha et al, 2015). The latter is known as lipodystrophy syndrome (LD) and can be present as the following subtypes: lipoatrophy (LA), which consists of peripheral subcutaneous fat loss; lipohypertrophy (LH), when there is adipose tissue accumulation, mainly central fat gain. It is possible, to observe both phenotypes simultaneously, namely mixed lipodystrophy (Guaraldi et al, 2013). LD prevalence is highly variable among studies due to the lack of consensus regarding its definition, diagnostic methods, genetic background, antiretroviral (ARV) drugs scheme, and lifestyle factors (Alves, 2014)

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