The ACE gene has received substantial attention in recent years as candidate for a variety of diseases. The most common polymorphism in ACE gene is the insertion-deletion (I/D) polymorphism located in intron 16. The D allele is associated with higher levels of ACE, and it is considered to be a risk factor for development diseases such as coronary artery disease, hypertension, type 2 diabetes, or related complications (1). Recently, the presence of the metabolic syndrome (MS), according to World Health Organization (WHO) criteria (2), was associated with the D allele in Chinese patients with type 2 diabetes (3). The authors found that patients with MS were more often carriers of the D allele (DD/ID) than the patients without the MS (58 vs. 42%, P < 0.01). The prevalence of MS in this sample of Chinese diabetic patients was 75%. The observation that the D allele is associated with the MS is an interesting finding, suggesting that the MS components (glucose homeostasis abnormalities and/or insulin resistance, hypertension, dyslipidemia, obesity, and/or microalbuminuria) might share a common genetic predisposition. We genotyped the ACE I/D polymorphism in 643 type 2 diabetic patients originally from the state of Rio Grande do Sul in the southernmost part of Brazil. Of the 643 subjects, 86% of the state population is from European ancestry and self-classified as white (4); 4 and 8.4% are black and mixed-race, respectively (4). Type 2 diabetes and MS diagnosis followed WHO definitions (2). The ACE genotyping was done as previously reported (5). The prevalence of carriers (DD/ID) and noncarriers of the D allele (II) was compared among the patients with and without the MS.

The MS prevalence in our sample was 75% and did not differ between white subjects and nonwhite subjects. The genotypes were in Hardy-Weinberg equilibrium (DD 30%; ID 50%; and II 20%). In the total group, the frequency of the carriers of the D allele among patients with MS was similar to that of those without MS (81 vs. 76%, P = 0.18). It also did not differ among white subjects (81 vs. 76%, P = 0.19) and nonwhite subjects (80 vs. 77%, P = 0.69). The power of our study to detect an association of the same magnitude as described by Lee and Tsai (3) was >95%. There were also no differences regarding age, duration of diabetes, proportion of males, or any other feature of the MS between carriers or noncarriers of the D allele.

At first glance, an apparent explanation for the discrepancy between our results and those reported by Lee and Tsai (3) would be due to ethnic reasons, as a result of I/D polymorphism interaction with other DNA sequence changes or environmental factors. It is well known that the allele frequency of ACE I/D polymorphism varies according to the ethnic group (6). The D allele is less frequent among Asian subjects than Caucasian subjects. In fact, the allele frequency in our sample of white individuals was higher than the Chinese study (33 vs. 55%, P = < 0.01), and it was similar to that described among other Caucasian populations (6). We do not believe that ethnic factors explain the differences between the two studies. If the ACE gene had a major role in MS predisposition, we would expect to observe lower prevalence of MS among Chinese patients than among Caucasian patients. Nevertheless, the prevalence was almost identical in both studies. An alternative hypothesis, still too complex to be proved, would be that the association reported in the Chinese study was found by chance and not casually related to the development of the syndrome. Further studies in other populations will be very informative in this regard.

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Address correspondence to Jorge L. Gross, Hospital de Clinicas de Porto Alegre, Servico de Endocrinologia, Rua Ramiro Barcellos 2350/Predio 12-4o. Andar, Porto Alegre, RS, Brazil 90035-003. E-mail: