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Genes of the Renin–Angiotensin System and the Development of Obesity in Men FREE

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The summary below is from the full report titled “Genetic Variation in the Renin–Angiotensin System and Abdominal Adiposity in Men: The Olivetti Prospective Heart Study.” It is in the 7 January 2003 issue of Annals of Internal Medicine (volume 138, pages 17-23). The authors are P Strazzullo, R Iacone, L Iacoviello, O Russo, G Barba, P Russo, A D'Orazio, A Barbato, FP Cappuccio, E Farinaro, and A Siani.


Ann Intern Med. 2003;138(1):I-26. doi:10.7326/0003-4819-138-1-200301070-00003
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What is the problem and what is known about it so far?

Both inherited factors (genes) and environmental factors (food and exercise) play a role in obesity. It is likely that many genes are involved in the growth of fat cells and obesity, but we are just beginning to learn about the relationships between particular genes and obesity. The renin–angiotensin system helps to regulate blood pressure through the action of proteins, including angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin receptors. Laboratory studies suggest that the renin–angiotensin system also affects the growth of fat cells. For this reason, some have wondered whether variations, called polymorphisms, in the genes of the renin–angiotensin system are related to obesity.

Why did the researchers do this particular study?

To find out whether variations (polymorphisms) in the genes of the renin–angiotensin system are related to obesity.

Who was studied?

959 Italian men, 25 to 75 years old, who worked for the Italian company Olivetti and were participating in a large study of risk factors for heart disease, the Olivetti Prospective Heart Study.

How was the study done?

Study participants had physical examinations that included weight, height, and waist measurements, and they supplied blood samples. Using the blood samples, the researchers determined each man's genetic makeup for three genes of the renin–angiotensin system: the ACE gene, the AGT gene, and the angiotensin II type I receptor (AT2R1) gene. They then looked for associations between the forms of these three genes and being overweight (defined by a measure that considers weight and height) or having abdominal obesity (defined by waist measurement). Of the 959 men, 314 had information from 1975 through 1995, enabling the researchers to examine the development of obesity over 20 years in relationship to the renin–angiotensin genes.

What did the researchers find?

The researchers found no association between the AGT or AT2R1 genes and body size or blood pressure. However, men whose ACE gene was the ACE DD form were more frequently overweight than men with the I/D or II forms of this gene. In addition, among the 314 men followed for 20 years, those with ACE DD were more than twice as likely to become overweight over the 20 years as men with ACE I/D or ACE II.

What were the limitations of the study?

This study included only Italian men, and the results may not apply to other types of patients. The researchers looked only at a small set of genes, and the effects of these genes were relatively small and probably represent only a small portion of the influence of genes on body size.

What are the implications of the study?

The findings of this study suggest that the renin–angiotensin system plays a role in the development of obesity.

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