Glutamate-Cysteine-Ligase Gene Polymorphisms are Associated with Cystic Fibrosis Lung Disease

Terrance J. Kavanagh, Ph.D.
Department of Environmental and Occupational Health Science, University of Washington
P30ES07033 and P42ES04696

NIEHS-supported scientists report that a polymorphism in a gene that regulates glutathione synthesis influences the severity of cystic fibrosis lung disease. The research team examined the genetic makeup of 440 subjects with cystic fibrosis. They found that polymorphisms in the glutamate-cysteine ligase catalytic subunit (GCLC) gene were associated with lung function in subjects with a milder form of the defective gene that causes cystic fibrosis.

Cystic fibrosis is a genetic disease affecting approximately 30,000 children and adults in the United States. A defective gene, known as the cystic fibrosis trans-membrane conductance regulator (CFTR) causes the body to produce abnormally thick, sticky mucus that clogs the lungs and can lead to life-threatening lung infections. Every year about 1000 people are diagnosed with the disease in the U.S. Life expectancy is generally shorter for people with the disease although medical advancements have prolonged life for many.

This finding demonstrates that lung disease severity in people with cystic fibrosis is mediated by factors that regulate levels of glutathione in the lung. The authors conclude that treatments that increase lung levels of glutathione may reduce the decline in lung function seen in patients with cystic fibrosis, especially those with the milder form of the mutation.

Citation: McKone EF, Shao J, Frangolias DD, Keener CL, Shephard CA, Farin FM, Tonelli MR, Pare PD, Sandford AJ, Aitken ML, Kavanagh TJ. Variants in the glutamate-cysteine-ligase gene are associated with cystic fibrosis lung disease. Am J Respir Crit Care Med. 2006 Aug 15;174(4):415-9.