Enzyme Gene and Longevity in the Xinjiang Uighur Autonomous Region of China: An Association Study
Dolkun Rahmutula,1,3 Tomohiro Nakayama,1 Yoichi Izumi,1 Yukio Ozawa,1 Hiroaki Shimabukuro,1 Hiroshi Kawamura,2 Shi Zhen-Wang,3 Jing Xiong-Wang,3 Muhupul Aisa,3 Chun Run-Yang,3 Masum Mahmut,3 Rena Mahsut,3 and Zhu Hen-Chen3
1 The Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, 2Department of Medicine, Nippon Dental University School of Dentistry, Tokyo. 3Department of Medicine, Xinjiang Medical University, Xinjiang Uighur Autonomous Region, the People's Republic of China.

Background: Longevity can be regarded as a multifactorial trait that results from an interaction between environmental factors and sets of epistatic alleles that have pleiotropic age-dependent effects. The Hotan district in the Xinjiang Uighur Autonomous region of China is relatively isolated and is well known for an ethnic group that displays marked longevity.

Methods: We performed a correlation study between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and longevity by comparing distributions of the polymorphism between three different ethnic groups in this region. We obtained data from 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects actually comprised two different age groups: those ranging in age from 59 to 70 years (Uighur older group in Hotan [UOH]) and those ranging in age from 90 to 113 years (Uighur longevity group in Hotan [ULH]). Genomic DNA was extracted from peripheral white blood cells. Polymerase chain reaction was performed to amplify the I/D polymorphic region of the ACE gene.

Results: Frequencies of the insertion (I) and deletion (D) alleles were 0.596 (243/408) and 0.404 (165/408) in the Uighur group, 0.606 (130/216) and 0.394 (85/216) in the Kazakh group, and 0.657 (117/178) and 0.343 (61/178) in the Han group. The overall distributions of alleles in these three groups did not differ significantly (χ² = 4.6, p = .33). Within the Uighur group, frequency of the D allele was significantly higher in the ULH group (0.448) than in the UOH group (0.355) (p = .04).

Conclusions: This association reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity. Our data may help elucidate the relationship between natural longevity and race differences among individuals in the Xinjiang Uighur Autonomous region of China.

ACE occurs in intron 16 (9). The insertion (I) allele contains a 287 bp Alu repeat sequence, whereas the deletion (D) allele lacks the Alu sequence. The D allele of the ACE gene has been associated with myocardial infarction (MI) (1012), cardiomyopathy (13,14), left ventricular hypertrophy (15), and coronary risk in non-insulin-dependent diabetic patients (16). In some studies, elevated ACE levels were associated with the D allele (11,17,18). Although associations between ACE polymorphism and cardiovascular diseases have been elucidated in many studies, they are neither strong nor consistent in all populations. Also, the allelic frequencies of the ACE gene vary between racial and ethnic groups. More surprising is the increased frequency of the ACE/D allele found in association with longevity (19). In this study, we made a correlation between the I/D polymorphism of the ACE gene and longevity by comparing distributions of the polymorphism between three ethnic groups, one of which is characterized by longevity, as well as that in control subjects.

The Xinjiang Uighur Autonomous Region of China is a relatively isolated area and is well known for an ethnic group that displays marked longevity, a group known as the Uighur (13). Angiotensin-converting enzyme (ACE), one of the constituents of the renin-angiotensin system, has attracted attention in the pathogenesis of cardiovascular disease. Cardiovascular disease is a multifactorial disease in which genetic and environmental factors play important roles. These factors may differ according to race or ethnic group. A number of studies have suggested various risk factors in association with cardiovascular diseases (4). Because it modulates the production of angiotensinThe processed text is as follows:

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