Genetic polymorphisms by deletion in genes that encode for glutathione S-transferases are associated with nicotine dependence and tobacco use-related medical disorders.

OBJECTIVE: We examine the relationship between nicotine dependence (ND) and ND-related medical disease and polymorphisms by deletion in genes that encode glutathione S-transferases (GSTs), e.g. GSTM1 and GSTT1. Individuals with homozygous gene deletions show deficiencies in GSTs enzyme activities impairing detoxification.

METHODS: This study comprised 182 tobacco users and 182 controls (neversmokers). GSTM1 and GSTT1 polymorphisms were assessed using a Multiplex- PCR based protocol.

RESULTS: Logistic regression analyses showed a significant association between ND and the GSTM1 and GSTT1 null genotypes. There were no significant associations between GSTT1, GSTM1 and GSTT1/M1 genetic variants and the Fagerström test for ND, age at onset, smoking cessation or a family history of ND. Patients with ND had increased rates of a family ND history and an increased prevalence of cardiovascular disease, hypertension, and lung disease. The null genotypes were associated with hypertension (i.e. GSTT1 × ND interaction), diabetes type 2 (i.e. GSTM1 × GSTT1 interaction), lung disease (i.e. GSTM1 × ND interaction) and cancer (i.e. GSTT1). The results show that GST null genotypes may confer protection against ND while they increase risk towards ND-related medical disorders.