Gene variant connected with lung function and risk of COPD

A variant of the gene encoding the MMP12 protein is associated with increased lung function in children with asthma and in adult smokers. It is also associated with a decreased risk of chronic obstructive pulmonary disease (COPD) by 35 percent in adult smokers, according to an international study published in New England Journal of Medicine.

Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway diseases that involve chronic inflammation of the lower respiratory tract. In the current study the researchers investigated the association between lung function and single-nucleotide polymorphisms (SNPs) in the gene encoding the pro-inflammatory protein matrix metalloproteinase 12 (MMP12). The study was conducted in cohorts that included both children and adults.

The research team first found that a functional variant in the promoter of the MMP12 gene was positively associated with the forced expiratory volume (FEV) in children with asthma. They also observed that this variant was associated with increased FEV in adult current and former smokers, but not in adults who had never smoked. Finally, they found an association between the same MMP12 gene variant and a reduced risk of COPD in adult cohorts.

The study was partly based on the Swedish BAMSE cohort, and researchers from Karolinska Institutet contributed to the findings. The study was lead by researchers at Harvard Medical School and Brigham & Women’s Hospital in the US.


Hunninghake, GM, Cho MH, Tesfaigzi Y, Soto-Quiros ME, Avila L, Lasky-Su J, Stidley C, Melén E, Söderhäll C, Hallberg J, Kull I, Kere J, Svartengren M, Pershagen G, Wickman M, Lange C, Demeo DL, Hersh CP, Klanderman BJ, Raby BA, Sparrow D, Shapiro SD, Silverman EK, Litonjua AA, Weiss ST, Celedón JC

MMP12, Lung Function and COPD in High-Risk Populations

N Engl J Med 2009: 391 (December 16, 2009)