Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

Area of Science:

• Environmental and Genetic Epidemiology
• Pulmonary Medicine
• Toxicology

Background:

• Understanding environmental and genetic factors is crucial for preventing chronic obstructive pulmonary disease (COPD).
• Glutathione S-transferase (GST) gene deficiency has been linked to poorer lung function in specific populations.
• This study investigates GST gene variants' association with accelerated lung function decline in the general adult population.

Purpose of the Study:

• To assess the association between low activity variants in Glutathione S-transferase (GST) genes and accelerated lung function decline.
• To identify genetic risk factors for lung function decline in the general adult population.
• To explore potential prevention strategies for chronic obstructive pulmonary disease (COPD).

Main Methods:

• Prospective cohort study (SAPALDIA) with 4686 participants.
• Multiple regression analysis examined polymorphisms in GSTM1, GSTT1, and GSTP1 genes.
• Longitudinal assessment of lung function decline (FEV1, FVC, FEF25-75) over 11 years, with analysis of effect modification by smoking, gender, and other factors.

Main Results:

• GST genotypes showed associations with lung function decline, most consistently for FEV1 (Forced Expiratory Volume in 1 second).
• GSTT1 homozygous gene deletion, alone or with GSTM1 deletion, was associated with accelerated FEV1 decline in men, but not women.
• Men with combined GSTT1 and GSTM1 gene deletions experienced an additional mean annual FEV1 decline of -8.3 ml/yr, comparable to the effect of persistent smoking.

Conclusions:

• Genetic deficiency in GSTT1 is a significant determinant of accelerated lung function decline in the general male population.
• These findings highlight the role of specific genetic variations in respiratory health.
• The results contribute to understanding COPD pathogenesis and identifying at-risk individuals.