J Thorac Cardiovasc Surg 2006;132:988
© 2006 The American Association for Thoracic Surgery
Candidate gene association analysis of 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
To the Editor:
In their recent article, Chen and colleagues1
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 polymorphisms (A-8202G) was found to be associated with the disease phenotypes of aortic aneurysm and aortic dissection. Such genetic association studies are based on the presence of linkage disequilibrium in the human genome and can be a powerful tool to dissect the genetic basis of diseases. A fundamental aspect of this approach, however, is the meticulous selection and matching of unrelated study subjects (case and control subjects). We believe that this study has some basic weaknesses; hence the results should be viewed with caution.
First, Chen and colleagues1 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 comparison cannot yield any meaningful evidence. It is a common observation in genetic association studies that genetic markers have diverse, and in some cases even opposite, associations in different ethnic groups.2–4 The strength of linkage disequilibrium 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 colleagues1 should comment on the presence of Hardy-Weinberg equilibrium in the genotype distributions 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 design. Furthermore, if the genotypes at the three loci are in Hardy-Weinberg equilibrium in case and control subjects, then it will be interesting to see the prevalence of the various haplotypes in the study population 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.
 |
References
|
|---|
- Chen L, Wang X, Carter SA, Shen YH, Bartsch HR, Thompson RW, et al. A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (-8202A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection. J Thorac Cardiovasc Surg 2006;131:1045-1052.[Abstract/Free Full Text]
- Cao K, Hollenbach J, Shi X, Shi W, Chopek M, Fernandez-Vina MA. Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations. Hum Immunol 2001;62:1009-1030.[Medline]
- Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 1997;17:1067-1073.[Abstract/Free Full Text]
- Wang X, Fan Z, Huang J, Su S, Yu Q, Zhao J, et al. Extensive association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol 2003;23:328-334.[Abstract/Free Full Text]
Related Article
-
Reply to the Editor
- Li Chen, Xing Li Wang, Joseph S. Coselli, and Scott A. LeMaire
J. Thorac. Cardiovasc. Surg. 2006 132: 988-989.
[Extract]
[Full Text]
[PDF]
Top
References