Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic syndrome traits
- 1Human Genetics Division, Duthie Building, Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD, UK
- 2Developmental Origins of Health and Disease Division, MRC Epidemiology Resource Centre, School of Medicine, Southampton University Hospital, Tremona Rd, Southampton, UK
- Correspondence to: Professor Ian N M Day Human Genetics Division, Duthie Building, Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD, UK;
- Accepted 18 November 2004
- Revised 4 November 2004
Background: The renin angiotensin system is important in the regulation of vascular tone and fluid and electrolyte balance. The angiotensin converting enzyme gene (ACE) genotype has been shown to affect exercise response and glucose load response dependent on birth weight. Angiotensin II type I receptor (AGTR1) A1166C has previously been associated with the development of hypertension and coronary disease, but its metabolic effects have not been investigated.
Method:AGTR1 A1166C was genotyped by allele specific PCR in 378 individuals from Hertfordshire, UK, who had been characterised for metabolic syndrome traits.
Results: Genotype counts were: AA, 183; AC, 170; CC, 25, consistent with Hardy-Weinberg equilibrium. The CC genotype was associated with significantly lower body mass index (by 1.7 units) in men (p = 0.03), and the same magnitude effect in women with significant lower weight in both genders (p = 0.01), also lower waist circumference and waist-hip ratio (p = 0.01) in men, with a trend for lower waist circumference in women also. Additionally, the CC genotype and/or C allele was associated with lower fasting glucose and insulin, and 30 and 120 min glucose in men (respectively, p = 0.08, 0.04, 0.01, 0.06). Lower means of systolic blood pressure, pulse pressure, cholesterol, and fasting triglyceride were also observed for the CC genotype in both genders though these were not statistically significant.
Conclusions: The AGTR1 1166 CC genotype appears to predispose to favourable anthropometric and metabolic traits, relative to cardiovascular risk.
- ACE, angiotensin converting enzyme
- AGT II, angiotensin II
- AGTR1, angiotensin II type I receptor
- AGTR2, angiotensin II type II receptor
- BMI, body mass index
- CAD, coronary artery disease
- DN, diabetic nephropathy
- HW, Hardy-Weinberg
- I/D, insertion/deletion
- K-EDTA, ethylenediaminetetra-acetic acid potassium salt
- LD, linkage disequilibrium
- OGTT, oral glucose tolerance test
- RAS, renin angiotensin system
- RNAbp, RNA-binding protein
- SNP, single nucleotide polymorphism
- UTR, untranslated region
We thank the UK MRC and BHF for support. MRA is an Iranian Ministry of Health PhD Scholar.
Competing interests: none declared