Lung function loss, smoking, vitamin C intake, and polymorphisms of the glutamate-cysteine ligase genes

American Journal of Respiratory and Critical Care Medicine
M SiedlinskiH Marike Boezen

Abstract

Smoking-induced oxidative stress contributes to chronic obstructive pulmonary disease, a lung disease characterized by low lung function and increasing mortality worldwide. The counterbalance for this effect may be provided by, for example, increased intake of the antioxidant vitamin C or endogenously acting antioxidant enzymes like glutamate-cysteine ligase (GCL), which is responsible for glutathione biosynthesis. To investigate associations of functional polymorphisms in GCL subunits (GCLM and GCLC) with lung function level and its longitudinal course, with vitamin C and smoking habits as potential interactive factors. Two independent general population samples (Doetinchem, n = 1,152, and Vlagtwedde-Vlaardingen, n = 1,390) with multiple lung function (FEV(1), VC) measurements were genotyped for three polymorphisms (C[-129]T, C[-588]T, and a trinucleotide GAG repeat [TNR]) in the subunits of GCL. Genetic effects on lung function level and decline were estimated using linear regression and linear mixed effect models adjusted for confounders. Findings were further investigated for interactions with vitamin C intake in the Doetinchem cohort. GCLC polymorphisms were significantly associated with lower lung function levels in inter...Continue Reading

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