GSTM1 null‐allele polymorphism, oxidative stress and HIV disease progression in an HIV‐infected population

Abstract

ObjectiveTo examine the effects GSTM1 null‐allele polymorphism on oxidative stress (OS) and disease progression in HIV+ adults.MethodsGSTM1 genotype was determined by quantitative PCR. OS (mitochondrial 8‐oxo‐2′‐deoxyguanosine, and Complex I and IV) and HIV disease (CD4 count and viral load) markers were measured in 129 HIV+ adults. Those with BMI >;28kg/m2 were excluded. Gene copies were not quantified, thus the Hardy‐Weinberg formula was not applicable.ResultsFunctional GSTM1 occurred in 66% (62/94) Blacks, and 33% (11/33) of the Caucasians. Those with functional GSTM1 had higher CD4 count (β=5.55, p=0.04), and lower viral load (β=−1.11, p=0.001), and mitochondrial 8‐oxo‐2′‐deoxyguanosine (β−0.28, p=0.03). Complex I activity (β=7.53. p=0.04) was increased over time compared to those with null‐allele GSTM1, controlling for other variables affecting OS.ConclusionThe presence of a functional GSTM1 genotype is associated with improved antioxidant activity over time. GSTM1 null‐allele polymorphism appears to have a detrimental effect on immune function and viral load control, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene.Supported by NIDA