Effect of genetic variations in drug transporters, metabolizing enzyme and regulatory genes to the development of HIV-associated lipodystrophy.

Adipocytes play a crucial role in the metabolism of lipids and sugars. Their response varies depending on the circumstances or other factors influenced by physiological and metabolic stresses. People living with HIV (PLWH) experience different effects of HIV and Highly Active Antiretroviral Therapy (HAART) on their body fat. Some patients respond well to ART, while others taking the similar regimens do not. The genetic makeup of patients has been strongly linked to the variable responses to HAART among PLWH. The cause of HIV-associated lipodystrophy syndrome (HALS) is not well understood, but it may be influenced by genetic variations in the host. The metabolism of lipid effectively modulates plasma triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels in PLWH. Genes related to drug metabolism and transport play an important role in ART drugs transportation and metabolism. Genetic variation in metabolizing enzyme genes of ARV drug, lipid transport, and transcription factor related genes could interfere fat storage and metabolism contributing to the development of HALS. Hence we comprehended the impact of genes associated with transport, metabolism, and various transcription factors in metabolic complications, and their impact on HALS. Study using databases such as PubMed, EMBASE, and Google Scholar was conducted to understand the impact of these genes on metabolic complications and HALS. Present article discuss the changes in the expression and regulation of genes and their involvement in the lipid metabolism, lipolysis, and lipogenesis pathways. Moreover, the drug transporter, metabolizing enzyme, and various transcription factors alteration can lead to HALS. Single Nucleotide Polymorphisms (SNPs) in genes that play an essential role in drug metabolism, and drug and lipid transportation may also contribute to individual differences in the emergence of metabolic and morphological alterations during HAART treatment.