Mutations’ influence is independent of smoking behavior, according to PLoS Genetics paper.

A group of scientists have discovered two genetic markers that appear to put smokers at a higher risk of developing COPD. “We believe that smokers who have these two SNPs face a nearly two-fold increase in risk of developing COPD, when compared with those who do not have these gene variants,” says David Goldstein, Ph.D., at Duke Medical Center and the senior author of the study appearing in PLoS Genetics.

“We also believe that these two alterations directly affect how the lungs function and that they may actually mediate the risk of developing COPD.” Both the SNPs were located near a nicotine receptor on chromosome 15, which has already been associated with lung cancer and other respiratory disorders, the team reports.

Additionally, they did not find any association between the variants and number of cigarettes smoked, reinforcing the notion that these mutations’ influence risk independent of smoking behavior.

Until now, there has only been one biological marker associated with COPD: a deficit of the protein A1AT, according to the researchers. “But we know that A1AT deficiency appears in only one to two percent of people with COPD, so we were pretty sure that there had to be other genetic variants at work as well,” says Dr. Goldstein.

The team started by examining the genomes of 823 people with COPD and 810 smokers without COPD in Norway. They were looking for the presence of the 100 top genetic variations already documented in individuals with COPD enrolled in the family-based International COPD Genetics Network (ICGN). They then took the most frequently occurring alterations from that study and evaluated them in three additional, independent groups: patients in the U.S. National Emphysema Treatment Trial, individuals enrolled in the Boston Early-Onset COPD study, and a control group from the Normative Aging Study.

Duke and GlaxoSmithKline (GSK) funded the study. Goldstein is a paid consultant for GSK, which has a smoking cessation therapy in Phase II trials. Other investigators on this study came from Brigham and Women’s Hospital, the University of Bergen, the Genetics Research Institute, Munich, the Ullevaal University Hospital, the University of Nebraska, the Cambridge Institute for Medical Research, and the ICGN team.

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