The findings come from the first-ever genome-wide association study of COPD and suggest that those who carry the markers may be able to reduce their risk if they quit smoking before the first symptoms of COPD occur.
"The public health message would probably be 'quit before it's too late,'" says David Goldstein, Ph.D., director of the Institute for Genome Sciences Center for Human Genome Variation at Duke and the senior author of the study appearing in PLoS Genetics.
Chronic obstructive pulmonary disease is one of the leading causes of death worldwide. While smoking is the biggest risk factor, there is considerable variation among those who develop the disease. Genetics plays a role, but until now, there has only been one biological marker proven to be associated with COPD – a deficit of the protein A1AT, which has also been linked to the development of lung cancer.
"But we know that A1AT deficiency appears in only 1-2 percent of people with COPD, so we were pretty sure that there had to be other genetic variants at work, as well," says Goldstein.
To discover if that hunch might prove true, Goldstein led an international team of investigators in 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. 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.
The genome-wide association study revealed several genetic aberrations that might be linked to COPD. But after a series of statistical analyses, only two single letter changes in DNA - (called single nucleotide polymorphisms, SNPs, or "snips") emerged as significant. Both were located near a nicotine receptor on chromosome 15 that has already been associated with lung cancer and other respiratory disorders. The SNPs also appeared with significant frequency among members of the international COPD genetics and emphysema groups.
"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 Goldstein. "We also believe that these two alterations directly affect how the lungs function – that they may actually mediate the risk of developing COPD."
The authors also ran tests among those who developed COPD and those who did not to find out if there was any relationship between the variants and how much people smoked. They didn't find any association, reinforcing the notion that these variants influence risk independent of smoking behavior.
The findings represent the discovery of the first major locus contributing to COPD in the general population. While Goldstein says the discovery may well open new therapeutic windows, it may also prompt clinicians to take another look at how they assess health risk among smokers.
"While it is clear that choosing to smoke is one of the worst health decisions a person can make, we now know that choice is even worse for some people than others," Goldstein said. "Our study also suggests that familiar measures of risk such as packs per day or smoking years, while informative, tell only a part of the story. The rest of the story is all about genetics, and it is still being written."
Michelle Gailiun | EurekAlert!
Further reports about: > A1AT > COPD > DNA > Genetic clues > Genetics > Genom > Genome Sciences > Human Genome Variation > SNP > biological marker > chromosome 15 > chronic obstructive pulmonary disease > gene variant > genetic variant > genetic variation > lung cancer > nicotine receptor > single nucleotide polymorphisms > snips
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy