Genetic Variation in the Renin–Angiotensin System and Abdominal Adiposity in Men: The Olivetti Prospective Heart Study

7 January 2003 | Volume 138 Issue 1 | Pages 17-23

Background: The renin–angiotensin system is involved in adipocyte growth and differentiation and possibly in adipose tissue metabolism.

Objective: To investigate the association of polymorphism in the angiotensin-converting enzyme (ACE) I/D gene, angiotensinogen M235T gene, and angiotensin II type 1 receptor A1166C gene with body mass index, body fat pattern, and obesity-associated hypertension.

Design: Cross-sectional longitudinal study.

Setting: The Olivetti factories in Marcianise and Pozzuoli, suburbs of Naples, Italy.

Participants: 959 adult men, 25 to 75 years of age.

Measurements: Renin–angiotensin system polymorphism, anthropometric indexes, blood pressure, and serum glucose and insulin levels.

Results: No association was detected between angiotensinogen or angiotensin II type 1 receptor gene polymorphism and anthropometric indexes or blood pressure. For ACE I/D polymorphism, significant age–genotype interaction was detected on cross-sectional observation; the relation of body mass index, waist circumference, and diastolic blood pressure to age was significantly greater in persons with the DD genotype than in those with the ID or II genotype. Overweight and abdominal adiposity were more common in men with the DD genotype, particularly among older participants (51.1% vs. 36.5% and 33.1% vs. 22.0%, respectively). Odds ratios were 1.82 (95% CI, 1.16 to 2.87) for overweight and 1.76 (CI, 1.06 to 2.90) for abdominal adiposity. Among 314 untreated men first examined 20 years earlier, those with the DD genotype had greater age-adjusted weight gain (1.45 kg [CI, 0.12 to 2.78 kg]) and change in diastolic blood pressure (2.83 mm Hg [CI, 0.39 to 5.28 mm Hg]). The relative risk for overweight was 2.34 (CI, 1.32 to 4.15) among participants with the DD genotype versus those with the ID or II genotype.

Conclusions: The ACE I/D polymorphism was a significant predictor of overweight and abdominal adiposity in men. DD homozygosity was associated with larger increases in body weight and blood pressure in aging persons, as well as with higher incidence of overweight.

Editors' Notes Context Angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II receptor type I (AT2R1) are expressed in adipose tissue, but their role in obesity is unknown. Common polymorphisms involve the ACE gene on chromosome 17 (ACE I/D), the AGT gene on chromosome 1, and the AT2R1 receptor gene on chromosome 3. Contribution Among 959 adult Italian men, DD homozygosity in the ACE gene was associated with overweight (odds ratio, 1.82 [95% CI, 1.16 to 2.87]) and abdominal obesity (odds ratio, 1.76 [CI, 1.06 to 2.90]) compared with the genotypes I/D and II. It was also associated with increases in weight over 20 years. Polymorphisms of AGT and AT2R1 were unrelated to measures of body size. Implications These results suggest that the renin–angiotensin system plays a role in the development of obesity. –The Editors

 

Author and Article Information

From Federico II University of Naples Medical School, Naples, Consorzio Mario Negri Sud, Santa Maria Imbaro, and Institute of Food Sciences, CNR, Avellino, Italy; and St. Georges' Hospital Medical School, London, United Kingdom.

Acknowledgments: The authors thank Dr. A. Scottoni, Dr. U. Candura, and Ms. M. Bartolomei for organizing and coordinating the fieldwork and the workers of the Olivetti factories for their cooperation. They also thank Drs. E. Ragone, F. Stinga, and L. Russo for fieldwork; Dr. Antonella Venezia for laboratory support; and Mrs. Rosanna Scala and Grazia Fanara for editorial assistance.

Grant Support: By funds from MURST (Italian Ministry of University and of Scientific and Technological Research COFIN, 1998 and 2000).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Pasquale Strazzullo, MD, Department of Clinical and Experimental Medicine, Federico II University of Naples, via S. Pansini 5, 80131 Naples, Italy; e-mail, strazzul{at}unina.it.

Current Author Addresses: Drs. Strazzullo, Barbato, and Farinaro; Mr. Iacone; and Ms. O. Russo: Department of Clinical and Experimental Medicine, Federico II University of Naples, via S. Pansini 5, 80131 Naples, Italy.

Dr. Iacoviello and Ms. D'Orazio: Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, via Nazionale, Santa Maria Imbaro, 66030 Lanciano (Chieti), Italy.

Drs. Barba and Siani and Ms. P. Russo: Institute of Food Sciences, CNR, via Roma 52A/C, 83100 Avellino, Italy.

Dr. Cappuccio: St. Georges' Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom.

Author Contributions: Conception and design: P. Strazzullo, R. Iacone, L. Iacoviello, F.P. Cappuccio, E. Farinaro, A. Siani.

Analysis and interpretation of the data: P. Strazzullo, R. Iacone, L. Iacoviello, O. Russo, G. Barba, P. Russo, F.P. Cappuccio.

Drafting of the article: P. Strazzullo, R. Iacone, O. Russo.

Critical revision of the article for important intellectual content: P. Strazzullo, L. Iacoviello, G. Barba, P. Russo, F.P. Cappuccio, E. Farinaro, A. Siani.

Final approval of the article: P. Strazzullo, L. Iacoviello, P. Russo, F.P. Cappuccio, E. Farinaro, A. Siani.

Provision of study materials or patients: P. Strazzullo, A. D'Orazio, A. Barbato.

Statistical expertise: G. Barba, F.P. Cappuccio, A. Siani.

Obtaining of funding: P. Strazzullo.

Administrative, technical, or logistic support: R. Iacone, L. Iacoviello, A. D'Orazio.

Collection and assembly of data: O. Russo, A. Barbato.