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

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.

Prevalence of Dyslipidemia in HIV-Positive Women with HPV Coinfection: A Preliminary Study

“…Although HIV infection and its therapies have been associated with changes in adipose tissue and disorders of glucose and lipid metabolism that may prematurely increase the risk of cardiovascular disease [ 4 , 6 ], more recent data suggest that immune activation and inflammation of chronic HIV infection also play an important role [ 26 ]. Thus, metabolic changes have been of great concern in HIV-infected adults since the introduction of antiretroviral therapy.…”

Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals

“…Similarly, a case-control study in Ghana found single nucleotide polymorphisms in four candidate genes and their association with dyslipidemia among ART-treated HIV patients, main variants in APOA5 (rs662799) and LDLR (rs6511720), respectively [ 108 ]. In research with HIV patients with HAART from Brazil, the SNPs (rs2273773 T > C, rs12413112 G > A, rs7895833 A > G, rs12049646 T > C) from the sirtuin-1 (SIRT1) gene, a modulator of transcription factors involved in energy regulation, were not associated with lipodystrophy and MetS, but white individuals with prolonged HAART intake were more prone to develop lipodystrophy [ 109 ]. A systematic review showed no association between the polymorphisms in APOC3 and PPAR-γ with lipodystrophy; although, there was an association between the G allele of the homeostatic iron regulator (HFE) and protection against the development of lipoatrophy when compared with the reference C allele.…”

Antiretrovirals Promote Insulin Resistance in HepG2 Liver Cells through miRNA Regulation and Transcriptional Activation of the NLRP3 Inflammasome

“…Highly active antiretroviral therapy (HAART) has significantly decreased the HIV-infected population’s mortality [ 8 , 9 ]. However, clinical studies have indicated that the usage of HAART promotes MetS in PLWH [ 10 ], with at least 21% displaying insulin resistance [ 11 , 12 , 13 ]. Despite these findings, proper mechanisms of action surrounding the combinational usage of HAART remain elusive.…”