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Reliability of Angiotensin-Converting Enzyme Gene Polymorphism in Testing
- Masato Odawara, MD; and
- Kamejiro Yamashita, MD
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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.
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
