Functional genetic variants of glutathione S-transferase protect against serum ascorbic acid deficiency

Background: Glutathione S-transferases (GSTs) are detoxifying enzymes that contribute to the glutathione-ascorbic acid (vitamin C) antioxidant cycle. Objective: The objective was to determine whether GST genotypes modify the association between dietary vitamin C and serum ascorbic acid. Design: Nonsmoking men and women (n = 905) between 20 and 29 y of age were participants in the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for deletion polymorphisms in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. A 196-item food-frequency questionnaire was used to estimate vitamin C intake. Results: A gene-diet interaction on serum ascorbic acid was observed for GSTM1 (P = 0.04) and GSTT1 (P = 0.01) but not for GSTP1 (P = 0.83). The odds ratio (95% CI) for serum ascorbic acid deficiency (<11 μmol/L) was 3.20 (1.88, 5.44) for subjects who did not meet the Recommended Dietary Allowance of vitamin C compared with those who did. The corresponding odds ratios (95% CIs) were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42), respectively, for individuals with the GSTT1*1/*1 +*1/*0 (functional) and GSTT1*0/*0 (null) genotypes and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09), respectively, for the GSTM1*1/* 1+GSTM1*1/*0 and GSTM1*0/*0 genotypes. Conclusions: The recommended intake of vitamin C protects against serum ascorbic acid deficiency, regardless of genotype. Individuals with GST null genotypes had an increased risk of defi-ciency if they did not meet the Recommended Dietary Allowance for vitamin C, which suggests that the GST enzymes protect against serum ascorbic acid deficiency when dietary vitamin C is insufficient.