-344C/T Variant in the promoter of the aldosterone synthase gene (CYP11B2) is associated with metabolic syndrome in men.

BACKGROUND The -344C/T variant in the promoter of the aldosterone synthase gene (CYP11B2) has been associated with hypertension and may influence glucose homeostasis and body mass in humans. We assessed the association between this genetic variant and metabolic syndrome in a large sample of European population. METHODS Eight hundred two male/female couples, recruited in the framework of the IMMIDIET study, a survey on cardiovascular risk in Italy, UK, and Belgium, had standardized measurements of body mass index, waist circumference, blood pressure (BP), serum total and HDL-cholesterol, triglycerides, and glucose and were genotyped for the -344C/T variant of CYP11B2. Metabolic syndrome was defined according to the International Diabetes Federation criteria. RESULTS The prevalence of the metabolic syndrome was 23.9% in men and 14.0% in women. The C allele of the variant was associated with metabolic syndrome in men (P = .002) but not in women. At logistic regression analysis, the odds ratio of metabolic syndrome increased progressively with the number of copies of the C allele (CT: 1.54, 95% CI from 1.01 to 2.35; CC: 2.25, 95% CI from 1.38 to 3.66) as compared with the TT homozygotes, taken as reference genotype. CONCLUSIONS The C allele of -344C/T variant of CYP11B2 increases susceptibility to metabolic syndrome in European men, but not in women, suggesting a pleiotropic role for this gene in modulating cardiovascular risk.

[1]  M. Ermani,et al.  Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. , 2006, The Journal of clinical endocrinology and metabolism.

[2]  R. Elston,et al.  Plasma Aldosterone Is Independently Associated With the Metabolic Syndrome , 2006, Hypertension.

[3]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[4]  F. Cappuccio,et al.  HindIII(+/-) polymorphism of the Y chromosome, blood pressure, and serum lipids: no evidence of association in three white populations. , 2006, American journal of hypertension.

[5]  P. White,et al.  Editorial: polymorphisms in CYP11B genes and 11-hydroxylase activity. , 2005, The Journal of clinical endocrinology and metabolism.

[6]  F. Cappuccio,et al.  Aldosterone synthase gene (CYP11B2) C-344T polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population , 2004, Journal of hypertension.

[7]  A. Siani,et al.  Tackling the genetic bases of metabolic syndrome: a realistic objective? , 2006, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[8]  David Botstein,et al.  Genetic variation in aldosterone synthase predicts plasma glucose levels , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  F. Cappuccio,et al.  Interaction between the C(−344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study , 2002, Journal of hypertension.

[10]  F. Buntinx,et al.  Dietary habit profile in European communities with different risk of myocardial infarction: the impact of migration as a model of gene-environment interaction. The IMMIDIET Study. , 2001, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[11]  Arya M. Sharma,et al.  The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome? , 2003, The international journal of biochemistry & cell biology.

[12]  J. Shaw,et al.  Metabolic syndrome—a new world‐wide definition. A Consensus Statement from the International Diabetes Federation , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[13]  T. Deguchi,et al.  Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas. , 2005, The Journal of clinical endocrinology and metabolism.

[14]  J. Connell,et al.  The impact of polymorphisms in the gene encoding aldosterone synthase (CYP11B2) on steroid synthesis and blood pressure regulation , 2004, Molecular and Cellular Endocrinology.

[15]  B. Egan,et al.  Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering. , 1994, American journal of hypertension.

[16]  E. Lander,et al.  Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease , 2003, Nature Genetics.

[17]  L. Kuller,et al.  Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial. , 2006, Diabetes care.

[18]  E. Davies,et al.  CYP11B2 polymorphisms and cardiovascular risk factors. , 2003, Journal of hypertension.