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

1 1 2 1 Ivana Beatrice Maˆnica Da Cruz, Graziela Oliveira, Maristela Taufer, Ney Furhmann Leal, 2 2 1 1 Carla Helena Schwanke, Luiz Glock, Yukio Moriguchi, and Emilio Hideyuki Moriguchi

1Instituto de Geriatria e Gerontologia, Pontif´ıcia Universidade Cato´lica do Rio Grande do Sul, Brazil. 2Faculdade de Biocieˆncias, Pontif´ıcia Universidade Cato´lica 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 of such studies are warranted, as further investigation in this area will have a high clinical relevance to cardiovascular disease and aging research.

polymorphism association with longevity, but did not con- firm an association with ACE polymorphism (7).

there gene polymorphisms that are truly longevity associated? In past decades, this question has become the main focus of several research groups studying longev- ity 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).

the data obtained were compared according to different methodological designs, generally comparing the allele and genotype frequency between a young group (20 or 30 years old) and a much older group (nonagenarians or centenar- ians). 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 asso- ciation 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 myo- cardial infarction suggested that limitations of the avail- able data still exist.

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

M ETHODS

Another study conducted in 10,150 individuals in the Danish population examined the association of ACE poly- morphism with ischemic heart disease and longevity. The authors did not find any association between ACE poly- morphism and longevity, with 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 anal- ysis. 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, Verano´polis, and Porto Alegre, Rio Grande do Sul, Brazil.

I/I DNA D/D I/DMarkerme §=490 bpmee =190 bp 

Figure 1. Angiotensin-converting enzyme (ACE) genotypes. Polymerase chain reaction amplification of ACE alleles insertion (I) and deletion (D) showed the presence of 490 bp and 190 bp products on 1.5% agarose gel electrophoresis.

The Japanese population came to Brazil’s southern re- gion after World War II (1950–1960) from several Japanese cities, mainly Nagasaki and Kumamoto. All Japanese par- ticipants included in this study were born in Japan or had both parents who were born in Japan (without any other ethnic miscegenation). The participants were recruited from the Japanese Assistant Association by random selection. All participants underwent a general physical examination. Blood samples were collected to confirm general health and to prepare DNA. The participants studied were not genetically related. The GP participants ranged in age from 10 to 104 years, and JP participants ranged in age from 20 to 100 years.