Published online before print March 31, 2009, doi: 10.1161/CIRCGENETICS.109.857359
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Original Articles |
A Common Variant of the FTO Gene Is Associated With Not Only Increased Adiposity but Also Elevated Blood Pressure in French Canadians
From the Brain and Body Centre (Z.P., C.S., T.P.), University of Nottingham, Nottingham, United Kingdom; Research Centre-CHUM (Z.P., O.S., J.T., P.H.), Montréal, Canada; McGill University (M.A., Y.X.), Montreal, Canada; Montreal Neurological Institute (G.T.L., T.P.), McGill University, Montreal, Canada; Groupe ECOBEs (M.P., S.V.), Jonquière, Canada; Université du Québec à Chicoutimi (L.R.), Quebec, Canada; MRC Centre for Causal Analyses in Translational Epidemiology (D.S.), University of Bristol, Bristol, United Kingdom; and Community Genomic Centre (D.G.), Université de Montréal, Chicoutimi Montreal, Canada.
Correspondence to Zdenka Pausova, MD, Brain and Body Centre, University of Nottingham, Nottingham, NG7 2RD, United Kingdom. E-mail zdenka.pausova{at}nottingham.ac.uk
Received November 12, 2008; accepted March 20, 2009.
Background— FTO is the first gene established as contributing to common forms of obesity. The gene is highly expressed in the hypothalamus and is thought to mediate this effect through its influence on energy homeostasis. The hypothalamus, however, also regulates blood pressure (BP). Therefore, we investigated whether the FTO-risk variant is associated not only with increased adiposity but also with elevated BP and whether the latter may be mediated, in part, by increased sympathetic modulation of vasomotor tone.
Methods and Results— The primary study was carried out in 485 adolescents recruited from a French Canadian founder population who underwent detailed body-composition and cardiovascular phenotyping. Body fat was examined with MRI, bioimpedance, and anthropometry. BP was recorded beat to beat at rest and during physical and mental challenges. Sympathetic modulation of vasomotor tone was assessed with power spectral analysis of BP. We found that individuals with the FTO-risk genotype compared with those without it demonstrate greater adiposity, including the amount of intra-abdominal fat (by 38%). They also showed higher systolic BP throughout the entire protocol, with a maximum difference during a mental stress (6.4 [1.5 to 11.3] mm Hg). The difference in BP was accompanied by elevated index of sympathetic modulation of vasomotor tone. A replication in an independent sample of adults from the same founder population confirmed the association between FTO and BP.
Conclusions— These results suggest that, in a French Canadian founder population, FTO may increase not only risk for obesity, as demonstrated in other populations, but also for hypertension. The latter may be related, at least in part, to the regulation of sympathetic vasomotor tone.
Key Words: genetics • hypertension • obesity • sympathetic nervous system • genetic association