Association between the APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), and MMP1 (rs1799750) gene polymorphisms and lipodystrophy in people living with HIV receiving antiretroviral therapy

The pathogenesis of lipodystrophy in people living with HIV (PLWHIV) receiving antiretroviral therapy (ART) appears to be multifactorial and may involve genetic factors; however, it is not yet fully understood. OBJECTIVE: To verify the association between single nucleotide polymorphisms (SNPs) in the APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), and MMP1 (rs1799750) genes and lipodystrophy and its subtypes in PLWHIV receiving ART. This analytical cross-sectional study defined lipodystrophy based on self-reports. Genotyping of the selected polymorphisms was performed using real-time polymerase chain reaction (RT-PCR). Among the 404 participants, 204 (51%) reported lipodystrophy, including 89 (43%) with mixed lipodystrophy, 72 (35%) with lipohypertrophy, and 43 (22%) with lipoatrophy. No association was observed between the APOC3, HFE, and MMP1 SNPs and the presence of lipodystrophy or its subtypes. However, the frequency of the AA genotype (<i>p</i> = 0.004 OR = 3.33, CI = 1.52-7.29) and the A allele (<i>p</i> = 0.031, OR = 1.72, CI = 1.08-2.75) of the ESR2 SNP was higher in individuals with lipoatrophy compared to those without lipodystrophy. In the multivariate analysis, a viral load &gt; 40 copies/mL (<i>p</i> = 0.037, OR = 2.52, CI = 1.03-6.91) and the current use of zidovudine (AZT) (<i>p</i> = 0.007, OR = 2.97, CI = 1.32-6.54) were associated with lipoatrophy. Participants with lipoatrophy exhibited a higher frequency of the AA genotype and the A allele of the rs3020450 SNP in the ESR2 gene. In addition, a viral load &gt; 40 copies/mL and the current use of AZT were independently associated with lipoatrophy, suggesting a potential involvement of this genetic variant, along with these clinical and laboratory cofactors, in the pathogenesis of lipoatrophy in PLWHIV receiving ART.