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Mar 26, 2009

Gene Variants Found that Affect Lung Function, Growth, and Susceptibility to Smoke

  • Researchers at the University of Southern California have found that a tiny variation within a single gene can determine how quickly and well lungs grow and function in children and adolescents in addition to showing how susceptible those children will be to exposure to second-hand tobacco smoke, even in utero.

    The scientists looked at the glutathione-s transferase (GST) class of genes, known to be involved in antioxidant defense. “Overall, we found that variation in several of the GST genes was important,” according to Carrie Breton, Sc.D., lead author of the study. “This was particularly true for children of mothers who had smoked during pregnancy.” The researchers suggest that the gene variants may not alter the development of the lung but instead its ability to defend itself against damage caused by free radicals.

    The team analyzed eight year’s worth of lung-function metrics and genotyping data from more than 2,100 children from two cohorts of fourth graders. The lung function measurements used were maximal mid expiratory flow rate (MMEF), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1).

    They specifically analyzed three haplotypes. For one gene, GSTM2, two variant patterns were researched. These patterns occurred in 30–35% of the white population. 

    One was found to promote stronger lung function, while the other variant correlated with poorer lung function and greater susceptibility to damage caused by maternal cigarette smoking during pregnancy. Moreover, the reduction in lung function was greater in children who had two copies of the variant pattern that reduced lung function compared to children with only one copy.

    Secondly, a haplotype in GSTM3, which occurred in 6–8% of the white population, showed a strong negative effect on MMEF.

    Finally, a haplotype in GSTM4, occurring in 16–22% of the population, showed significantly decreased rates of growth for FEV1, FVC, and MMEF. Like GSTM2, the reduction in lung function was greatest in children who had two copies of the variant pattern that reduced lung function.

    Moving forward the researchers may investigate how these genes interact with one another to jointly effect lung development. Future studies would also explore the timing and quantity of tobacco smoke exposure during pregnancy in combination with variation in the genes to further understand how they jointly affect fetal lung development.



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