Protective association of the HIF-1α rs11549465 polymorphism with metabolic syndrome in people living with HIV on antiretroviral therapy

Background People living with HIV (PLWH) receiving antiretroviral therapy (ART) are at increased risk of metabolic syndrome (MS). Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in metabolic regulation, and the functional polymorphism of HIF-1α rs11549465 (C1772T) may influence susceptibility to metabolic disturbances. This study aimed to investigate the association between the HIF-1α rs11549465 polymorphism and MS in PLWH on ART. Methods This multicentre cross-sectional study included 121 PLWH. Participants were classified as MS cases or controls according to NCEP ATP III criteria. Genotyping of the HIF-1α rs11549465 polymorphism was performed using Real-time PCR with a TaqMan assay. Clinical, metabolic, and HIV-related parameters were analysed. Multivariable logistic regression was used to identify independent factors associated with MS. Results MS was identified in 47 participants (38.8%), while 74 (61.2%) served as controls. The minor T allele frequency of HIF-1α rs11549465 was 24%. The presence of T allele and CT/CT+TT genotypes was associated with a significantly lower odds of MS ( p < 0.05). Among the participants with MS, carriers of CT+TT exhibited a lower prevalence of hypertension ( p < 0.05). The individuals with MS were older and had longer HIV infection duration and ART exposure ( p < 0.05). Stratified analysis indicated that the protective association of the CT genotype was more pronounced at shorter durations of HIV infection and shorter ART exposure ( p < 0.05). In multivariable analysis, elevated triglycerides and fasting glycemia were the strongest independent correlates of MS, while the HIF-1α rs11549465 CT+TT genotype remained independently associated with lower odds of MS ( p < 0.05). Conclusion The HIF-1α rs11549465 T allele and CT+TT genotypes are associated with a lower odds of prevalent MS and hypertension in PLWH receiving ART. This protective association remained evident after adjustment for established metabolic risk factors, although it appeared less pronounced with longer HIV infection and ART duration.