Angiotensin I-Converting Enzyme Gene Polymorphism in Two Ethnic Groups Living in Brazil's Southern Region: Association with Age

Ivana Beatrice Manica Da Cruz, Graziela Oliveira, Maristela Taufer, Ney Furhmann Leal, Carla Helena Schwanke, Luiz Glock, Yukio Moriguchi, and Emilio Hideyuki Moriguchi

Instituto de Geriatria e Gerontologia, Pontifícia Universidade Católica do Rio Grande do Sul, Brazil. Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Brazil.

Background: Several studies have been published on the association between ACE (angiotensin I-converting enzyme) polymorphism and longevity. However, the results are controversial.

Methods: We analyzed the association between ACE polymorphism and age in two different ethnic populations: a population originating from different European countries (Gaucha Population, GP) and a population originating from Japan (JP). Both populations live in Brazil's southern region.

Results: We determined the ACE genotype in 834 persons aged 10-104 years. The ACE genotype and allele frequencies differed between the two populations, with the D allele being more frequent in GP than JP. We found an association between the DD genotype and D allele and age in the GP group only. The ACE polymorphism-age association occurred at age 60 years in the GP population with decreasing II frequency.

Conclusion: We cannot dismiss the possibility of the association between ACE polymorphism and age involving linkage disequilibrium since the nature of this phenomenon is still controversial. From our studies, it appears that there is a correlation between age, ethnicity, and ACE polymorphism. More studies are warranted as further investigation in this area will have high clinical relevance to cardiovascular disease and aging research.

Polymorphism association with longevity but did not confirm an association with ACE polymorphism (7). Are there gene polymorphisms that are truly longevity associated? In past decades, this question has become the main focus of several research groups studying longevity and aging processes. In an effort to dissect the genetic components of longevity, several studies have described a connection between gene polymorphism and advanced age (1,2). If there is an association between ACE polymorphism and age, it is necessary to perform studies examining all ages to help us determine at which moment during aging ACE polymorphism could occur. Another point that needs to be clarified is whether age-associated ACE polymorphism is.

The angiotensin-converting enzyme (ACE) gene was investigated and, despite its connection with the deletion (D) allele in cardiovascular diseases, the frequency of this allele seemed to be greater in the oldest individuals (3). The excess of D allele of the ACE gene was, at first sight, apparently paradoxical because previous reports had suggested an association of the D allele with a predisposition to myocardial infarction (MI) (4). A meta-analysis made by Samani and colleagues (5) of the association of the D allele with myocardial infarction suggested that limitations of available data still exist.

In this article, we studied the change in ACE polymorphism frequency as a function of age in two different ethnic populations that live in Southern Brazil region.

Methods: Another study conducted in 10,150 individuals in the Danish population examined the association of ACE polymorphism with ischemic heart disease and longevity. The authors did not find any association between ACE polymorphism and longevity, with a change of DD frequency as a function of age in participants aged 20 to 80 years (6). However, a limitation of the study cited could be the noninclusion of nonagenarians and centenarians in the analysis. Another study that also examined the association of ACE and apolipoprotein E (ApoE) polymorphism with longevity in French centenarians observed only an ApoE.

Populations: A total of 834 participants aged 10 to 104 years were studied. The population examined was composed of individuals mixed from different ethnic groups [Native South American, European Caucasian (Portuguese, Italians, Spaniards, and Germans)] originating a new genetic pool termed here the Gaucha population (GP). Participants were recruited by random selection from the Health and Social Assistance Program of Gravatai, Veranopolis, and Porto Alegre, Rio Grande do Sul, Brazil.

ACE Genotyping: Genomic DNA was isolated from peripheral blood leukocytes by standard methods (8). ACE genotyping was performed using the method described by Schachter and colleagues (3). ACE amplification of DNA was performed by polymerase chain reaction (PCR) with 0.1 mg of the DNA extract and thermostable Taq polymerase (Gibco, Inc., San Diego, CA) according to the manufacturer's instructions. PCR was performed in a thermal reactor using oligonucleotide primers 5Weinberg equilibrium and comparing genotypic and allelic frequencies among ethnic groups were the objectives of this study. Statistical analysis showed that in the GP group, all ACE genotypes had similar ages until the 10th percentile, but from the 25th percentile, the age values for II were lower than for DD and ID genotypes. In the JP group, DD genotypes had age values lower than II and ID genotypes until the 50th percentile. The study also analyzed different cut-off points for ages ((cid:1)60, (cid:1)70, and (cid:1)80 years old) to determine when the frequency of D allele changed significantly. In GP, a D allele frequency increase was observed from (cid:1)60 years old. However, no significant differences were found among ACE genotype frequencies in JP at any age cut-points examined.