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

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.