The rs1799884 Glucokinase Gene Polymorphism Modulates Susceptibility to HIV Status and CD4 Cell Count and Viral Load before and After Treatment in AIDS Progressors.

Abstract

The human immunodeficiency virus (HIV), a retrovirus targeting the immune system and the primary agent causing acquired immunodeficiency syndrome (AIDS), can have fatal consequences. Although antiretroviral treatment has significantly reduced mortality and comorbidity in people living with HIV (PLHIV), its impact on metabolic syndrome (MetS) remains notable. Several genome-wide association studies have identified a link between the glucokinase gene (GCK) and MetS, particularly in type 2 diabetes. However, no studies have investigated the association between this gene and HIV status. Our study aims to evaluate the association of the rs1799884 polymorphism in the GCK gene with HIV status in a group of Moroccan patients. This case-control study includes 207 PLHIV and 181 HIV-uninfected controls. Genotyping of the rs1799884 polymorphism in the GCK gene was performed using a predesigned TaqMan single-nucleotide polymorphism genotyping assay. The genotypic distribution between PLHIV and HIV-uninfected controls revealed a significant difference. Patients with the CT genotype had a 4.47-fold increased risk of infection [odds ratio (OR) = 4.47; 95% confidence interval (CI) = 2.75-7.29; p = .001]. However, the TT genotype conferred protection against HIV in a recessive model (OR = 0.50; 95% CI = 0.28-0.91; p = .021). Interestingly, the risk associated with the CT genotype was even higher in AIDS-related cases (OR = 9.37; 95% CI = 4.32-20.36; p = .0001). Additionally, under the dominant model, individuals with CT and TT genotypes had a 7.67-fold increased risk of infection (OR = 7.67; 95% CI = 3.60-16.36; p < .0001). However, the TT genotype under the recessive model was not significantly associated with disease progression. No significant association was observed between these genotypes and CD4 count; however, there was a significant variation in viral load after treatment. Our findings suggest that the rs1799884-C/T variant of the GCK gene may influence susceptibility to HIV status, progression to AIDS, and response to treatment.