Letters to the Editor Candidate gene association analysis of thoracic aortic aneurysm and dissection To the Editor: In their recent article, Chen and col- leagues 1 have described the association of three single-nucleotide polymorphisms of the matrix metalloproteinase 9 gene, with thoracic aortic aneurysm and dissection. One of the three single-nucleotide poly- morphisms (A-8202G) was found to be as- sociated with the disease phenotypes of aortic aneurysm and aortic dissection. Such genetic association studies are based on the presence of linkage disequilibrium in the hu- man genome and can be a powerful tool to dissect the genetic basis of diseases. A fun- damental aspect of this approach, however, is the meticulous selection and matching of un- related study subjects (case and control sub- jects). We believe that this study has some basic weaknesses; hence the results should be viewed with caution. First, Chen and colleagues 1 compared the prevalence of alleles and genotypes at the three loci between patients recruited from the United States and their control subjects from Australia. In our opinion, the case and control subjects belong to two very distinct populations, and their com- parison cannot yield any meaningful evi- dence. It is a common observation in genetic association studies that genetic markers have diverse, and in some cases even opposite, associations in different eth- nic groups. 2-4 The strength of linkage dis- equilibrium between any two loci will not be equal in any two different ethnic groups, hence the importance of ethnicity-matched control subjects. Second, Chen and colleagues 1 should comment on the presence of Hardy- Weinberg equilibrium in the genotype dis- tributions at the three loci separately for the case and control groups. Hardy-Weinberg equilibrium in the genotype distributions provides evidence of random selection of subjects, which is an important pillar of the case-control genetic association study de- sign. Furthermore, if the genotypes at the three loci are in Hardy-Weinberg equilib- rium in case and control subjects, then it will be interesting to see the prevalence of the various haplotypes in the study popu- lation and also their associations with the diagnoses under study. This may provide additional information about the role of matrix metalloproteinase polymorphisms in thoracic aortic aneurysm and dissection. Usman Ahmad, MBBS Muhammad A. Javed, MD Saulat H. Fatimi, MD, FACS Department of Surgery Division of Cardiothoracic Surgery Faculty of Health Sciences Aga Khan University Karach; Pakistan References 1. Chen L, Wang X, Carter SA, Shen YH, Bar- tsch HR, Thompson RW, et al. A single nu- cleotide polymorphism in the matrix metallo- proteinase 9 gene (-8202A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection. J Thorac Cardiovasc Surg. 2006;131:1045-52. 2. Cao K, Hollenbach J, Shi X, Shi W, Chopek M, Fernandez-Vina MA. Analysis of the fre- quencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diver- sity in these loci and contrasting distribution patterns in these populations. Hum Immunol. 2001;62:1009-30. 3. Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arte- rioscler Thromb Vasc Biol. 1997;17:1067-73. 4. Wang X, Fan Z, Huang J, Su S, Yu Q, Zhao J, et al. Extensive association analysis be- tween polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol. 2003;23:328-34. doi:10.1016/j.jtcvs.2006.05.050 Reply to the Editor: We appreciate the comments by Ahmad and colleagues regarding our initial inves- tigation of single nucleotide polymor- phisms (SNPs) involving the matrix metal- loproteinase 9 gene (MMP9) in patients The Editor welcomes submissions for possible publication in the Letters to the Editor section that consist of commen- tary on an article published in the Jour- nal or other relevant issues. Authors should: ● Include no more than 500 words of text, three authors, and five references ● Type with double-spacing ● See http://jtcs.ctsnetjournals.org/misc/ ifora.shtml for detailed submission instructions. ● Submit the letter electronically via jtcvs.editorialmanager.com. Letters commenting on an article pub- lished in the JTCVS will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an opportunity to offer a timely response (2 weeks) to the letter. Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned. 988 The Journal of Thoracic and Cardiovascular Surgery ● October 2006