BACKGROUND: Variation in the Fat-Mass and Obesity-Associated (FTO) gene has been associated with obesity, diabetes, and hypertension. However, its association with cardiovascular disease (CVD) in healthy populations and any interaction with physical activity remain unclear. METHODS: The FTO rs8050136 allele was determined in a prospective cohort study of 21,674 apparently healthy White US women in the Women's Genome Health Study. RESULTS: During a mean follow-up of 12.7±2.0 years, 664 incident CVD events occurred. The risk allele (A) was associated with higher prevalence of hypertension, diabetes, and metabolic syndrome (all P<.05). In a multivariate model, there was significant association of the risk allele with CVD (hazard ratio [HR] per allele copy 1.14, 95% CI 1.01-1.28) that was no longer significant after additional adjustment for body mass index (BMI) (HR 1.10, 95% CI 0.97-1.23). There was statistical evidence of an interaction between FTO and physical activity (P=.048). We found a significant association of FTO with CVD only among less-active (≤8.8 metabolic equivalent-h/wk) women (HR 1.19, 95% CI 1.02-1.38) in multivariate analyses that included BMI. More-active women did not have this increased risk (HR 0.96, 95% CI 0.79-1.16]). In a model that adjusted for BMI, less-active/high-risk (A/A) women were at 54% increased risk of developing CVD (HR 1.54, 95% CI 1.13-2.11), compared to more-active/low-risk (C/C) women. CONCLUSIONS: Carriers of the FTO risk allele have an increased risk of CVD mediated by BMI. There appears to be an interaction with physical activity, such that this risk increase is only in less-active women.
RCT Entities:
BACKGROUND: Variation in the Fat-Mass and Obesity-Associated (FTO) gene has been associated with obesity, diabetes, and hypertension. However, its association with cardiovascular disease (CVD) in healthy populations and any interaction with physical activity remain unclear. METHODS: The FTOrs8050136 allele was determined in a prospective cohort study of 21,674 apparently healthy White US women in the Women's Genome Health Study. RESULTS: During a mean follow-up of 12.7±2.0 years, 664 incident CVD events occurred. The risk allele (A) was associated with higher prevalence of hypertension, diabetes, and metabolic syndrome (all P<.05). In a multivariate model, there was significant association of the risk allele with CVD (hazard ratio [HR] per allele copy 1.14, 95% CI 1.01-1.28) that was no longer significant after additional adjustment for body mass index (BMI) (HR 1.10, 95% CI 0.97-1.23). There was statistical evidence of an interaction between FTO and physical activity (P=.048). We found a significant association of FTO with CVD only among less-active (≤8.8 metabolic equivalent-h/wk) women (HR 1.19, 95% CI 1.02-1.38) in multivariate analyses that included BMI. More-active women did not have this increased risk (HR 0.96, 95% CI 0.79-1.16]). In a model that adjusted for BMI, less-active/high-risk (A/A) women were at 54% increased risk of developing CVD (HR 1.54, 95% CI 1.13-2.11), compared to more-active/low-risk (C/C) women. CONCLUSIONS: Carriers of the FTO risk allele have an increased risk of CVD mediated by BMI. There appears to be an interaction with physical activity, such that this risk increase is only in less-active women.
Authors: Scott M Grundy; James I Cleeman; Stephen R Daniels; Karen A Donato; Robert H Eckel; Barry A Franklin; David J Gordon; Ronald M Krauss; Peter J Savage; Sidney C Smith; John A Spertus; Fernando Costa Journal: Circulation Date: 2005-09-12 Impact factor: 29.690
Authors: I-Min Lee; Nancy R Cook; J Michael Gaziano; David Gordon; Paul M Ridker; Joann E Manson; Charles H Hennekens; Julie E Buring Journal: JAMA Date: 2005-07-06 Impact factor: 56.272
Authors: Shumin M Zhang; Steven C Moore; Jennifer Lin; Nancy R Cook; JoAnn E Manson; I-Min Lee; Julie E Buring Journal: Am J Epidemiol Date: 2005-12-07 Impact factor: 4.897
Authors: Paul M Ridker; Daniel I Chasman; Robert Y L Zee; Alex Parker; Lynda Rose; Nancy R Cook; Julie E Buring Journal: Clin Chem Date: 2007-12-10 Impact factor: 8.327
Authors: Camilla H Andreasen; Kirstine L Stender-Petersen; Mette S Mogensen; Signe S Torekov; Lise Wegner; Gitte Andersen; Arne L Nielsen; Anders Albrechtsen; Knut Borch-Johnsen; Signe S Rasmussen; Jesper O Clausen; Annelli Sandbaek; Torsten Lauritzen; Lars Hansen; Torben Jørgensen; Oluf Pedersen; Torben Hansen Journal: Diabetes Date: 2007-10-17 Impact factor: 9.461
Authors: A M Wolf; D J Hunter; G A Colditz; J E Manson; M J Stampfer; K A Corsano; B Rosner; A Kriska; W C Willett Journal: Int J Epidemiol Date: 1994-10 Impact factor: 7.196
Authors: James M Hagberg; Tuomo Rankinen; Ruth J F Loos; Louis Pérusse; Stephen M Roth; Bernd Wolfarth; Claude Bouchard Journal: Med Sci Sports Exerc Date: 2011-05 Impact factor: 5.411
Authors: Michael L Alosco; Andreana Benitez; John Gunstad; Mary Beth Spitznagel; Jeanne M McCaffery; John E McGeary; Athena Poppas; Robert H Paul; Lawrence H Sweet; Ronald A Cohen Journal: Psychogeriatrics Date: 2013-03 Impact factor: 2.440
Authors: Antti Huuskonen; Jani Lappalainen; Niku Oksala; Matti Santtila; Keijo Häkkinen; Heikki Kyröläinen; Mustafa Atalay Journal: PLoS One Date: 2012-12-17 Impact factor: 3.240
Authors: Rahul Kumar; Samantha Kohli; Perwez Alam; Ritankur Barkotoky; Mohit Gupta; Sanjay Tyagi; S K Jain; M A Qadar Pasha Journal: PLoS One Date: 2013-05-14 Impact factor: 3.240