LETTER
Reliability of Angiotensin-Converting Enzyme Gene Polymorphism in Testing
Masato Odawara, MD, and
Kamejiro Yamashita, MD
15 May 1997 | Volume 126 Issue 10 | Page 828
TO THE EDITOR:
Winkelmann and colleagues [1] reported that deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene is not associated with increased risk for myocardial infarction or coronary artery disease. Their findings are contradictory to those of many previous studies. It has also been reported that mistyping frequently occurs in the genotyping of the ACE gene [2]. Winkelmann and colleagues confirmed the genotypes by using polymerase chain reaction (PCR) and included dimetyl-sulfoxide in the reaction mixture. However, our recent observation indicates that confirmation of deletion polymorphism by this method also frequently leads to erroneous results [3].
By comparing various methods, we concluded that it is advisable to initially classify ACE genotypes by using PCR with insertion/deletion flanking primers and inclusion of dimethyl-sulforide. The DD genotype should then be confirmed by using insertion-specific primers to which dimethyl-sulfoxide has been added. With conventional methods, including the one that Winkelmann and colleagues adopted, the presence of the DD genotype is likely to be overestimated. In addition, the low rate of reproducibility with this method may result in erroneous support of a phenotype-genotype association. Although data on the association between deletion polymorphism and diabetic microvascular complications of hypertension [4] are often conflicting, the association between polymorphism and myocardial infarction has been noted in many previous reports [4, 5]. We think that the discrepancies between Winkelmann and colleagues' findings and those of these previous studies are at least partly attributable to the mistyping and low reproducibility that occur more frequently than has been previously believed, even with PCR mixtures to which dimetyl-sulfoxide has been added. We hope that other investigators reevaluate their data by using our method.
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Author and Article Information
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University of Oxford, Oxford, United Kingdom
University of Tsukuba, Ibaraki, Japan
1. Winkelmann BR, Nauck M, Klein B, Russ AP, Bohm BO, Siekmeier R, et al. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease. Ann Intern Med. 1996; 125:19-25.
2. Fogarty DG, Maxwell AP, Doherty CC, Hughes AE, Nevin NC. ACE gene typing. Lancet. 1994; 343:851.
3. Odawara M, Matsunuma A, Yamashita K. Mistyping frequency of the angiotensin-converting enzyme gene polymorphism and an improved method for its avoidance. Hum Genet. [In press].
4. Soubrier F, Nadaud S, Williams TA. Angiotensin I converting enzyme gene: regulation, polymorphism and implications in cardiovascular diseases. Eur Heart J. 1994; 15(Suppl D):24-9.
5. Iwai N, Ohmichi N, Nakamura Y, Kinoshita M. DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation. 1994; 90:2622-8.
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