n engl j med 362;13 nejm.org april 1, 2010 1241 correspondence The new england journal of medicine MMP12, Lung Function, and COPD in High-Risk Populations To the Editor: Hunninghake et al. (Dec. 31 is- sue) 1 report an association between single-nucle- otide polymorphisms (SNPs) in MMP12 and lung function in children with asthma and in adults who smoke, as well as an association with a re- duced risk of chronic obstructive pulmonary dis- ease (COPD) in adult smokers. However, a statis- tical genetic association may be observed when the implicated SNP is in strong linkage disequi- librium with another ungenotyped, but “causa- tive,” SNP, often one that is in close proximity to the implicated SNP. To determine whether their findings could be explained by linkage disequi- librium, the authors present data for neighboring genes MMP3 and MMP13. Surprisingly, the au- thors did not present data for MMP1 (encoding interstitial collagenase), which is adjacent to MMP3 on chromosome 11 and is closer to MMP12 than is MMP13 . Moreover, MMP1 has been strong- ly implicated in the pathogenesis of both COPD 2 and asthma. 3 It is a testable hypothesis that MMP1 encodes the protease that drives lung pathology. The association described by Hunninghake et al. could be attributable to SNPs within MMP1. Paul T. Elkington, M.D., Ph.D. Graham S. Cooke, M.D., Ph.D. Imperial College London London, United Kingtom p.elkington@imperial.ac.uk No potential conflict of interest relevant to this letter was re- ported. Hunninghake GM, Cho MH, Tesfaigzi Y, et al. 1. MMP12, lung function, and COPD in high-risk populations. N Engl J Med 2009;361:2599-608. D’Armiento J, Dalal SS, Okada Y, Berg RA, Chada K. Collag- 2. enase expression in the lungs of transgenic mice causes pulmo- nary emphysema. Cell 1992;71:955-61. Ohta Y, Hayashi M, Kanemaru T, Abe K, Ito Y, Oike M. Dual 3. modulation of airway smooth muscle contraction by Th2 cyto- kines via matrix metalloproteinase-1 production. J Immunol 2008; 180:4191-9. To the Editor: We wonder whether Hunning- hake et al. observed an association between the functional SNP in MMP12 and cardiovascular diseases in adult cohorts. An association between COPD and cardiovascular disease, due in part to systemic low-grade inflammation, has been re- ported, 1 and MMP12 is a mediator of inflamma- tion, remodeling, and plaque rupture in the vas- culature. We also wonder whether there is a genetic effect of this SNP on the interaction be- tween lung function and passive exposure to to- bacco smoke in the cohorts of children analyzed by the authors. Hiroyuki Morita, M.D., Ph.D. Ryozo Nagai, M.D., Ph.D. University of Tokyo Tokyo, Japan hmrt-tky@umin.net No potential conflict of interest relevant to this letter was re- ported. Sin DD, Man SF. Why are patients with chronic obstructive 1. pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstruc- tive pulmonary disease. Circulation 2003;107:1514-9. this week’s letters 1241 MMP12, Lung Function, and COPD in High-Risk Populations 1242 Sensitive Cardiac Troponin T Assay 1244 Discharge Planning and Rates of Readmissions 1245 Molecular Basis of Colorectal Cancer 1247 More on Integrated Delivery Systems 1248 Human Parvovirus B19–Associated Myocarditis The New England Journal of Medicine Downloaded from www.nejm.org on November 23, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved.