Lifestyle interaction with fat mass and obesity-associated (FTO) genotype and risk of obesity in apparently healthy U.S. women.
OBJECTIVE
Variation in the fat mass and obesity-associated (FTO) gene is associated with obesity. The extent to which separate and combined effects of physical activity and caloric intake modify this association remains unclear.


METHODS
FTO polymorphism rs8050136 was measured, and physical activity, caloric intake, and anthropometrics were self-reported in 21,675 apparently healthy Caucasian women.


RESULTS
The effect of the risk allele (A) on BMI was larger among inactive or higher intake women, with additive effects of inactivity and high intake on the associated genetic risk. Specifically, each A allele was associated with mean BMI difference of +0.73 (SE 0.08) kg/m(2) among inactive women (≤ median, 8.8 MET-hours/week), compared with +0.31 (0.06) kg/m(2), P < 0.0001, among active women (>8.8 MET-hours/week). Similarly, each A allele was associated with mean BMI difference of +0.65 (0.07) among high intake women (>median, 1,679 kcals/day), compared with +0.38 (0.07) kg/m(2), P = 0.005, among low intake women (≤ 1,679 kcals/day). Among inactive/high intake women, each A allele was associated with mean BMI difference of +0.97 (0.11) kg/m(2) vs. +0.22 (0.08) kg/m(2) among inactive/low intake women, P < 0.0001. Among inactive/high intake women, each A allele carried increased risk of obesity (odds ratio 1.39, 95% CI 1.27-1.52) and diabetes (odds ratio 1.36, 95% CI 1.07-1.73).


CONCLUSIONS
In this study, lifestyle factors modified the genetic risk of FTO on obesity phenotypes, particularly among women who were both inactive and had high intake. Healthier lifestyle patterns blunted but did not completely eliminate the associated genetic risk.
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Tariq
T
Ahmad
I-Min
IM
Lee
Guillaume
G
Paré
Daniel I
DI
Chasman
Lynda
L
Rose
Paul M
PM
Ridker
Samia
S
Mora
D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
JAMA. 2006 Mar 22;295(12):1412-9
16551713
Diabetes. 2008 Jan;57(1):95-101
17942823
N Engl J Med. 2008 Dec 11;359(24):2558-66
19073975
Obesity (Silver Spring). 2008 Nov;16(11):2472-80
18787525
Clin Chem. 2008 Feb;54(2):249-55
18070814
Arch Intern Med. 2008 Sep 8;168(16):1791-7
18779467
Am J Clin Nutr. 2009 Nov;90(5):1418-25
19726594
Diabetes. 2006 Oct;55(10):2856-62
17003353
Circulation. 2006 Jun 27;113(25):2943-6
16801475
Am J Clin Nutr. 2006 Jul;84(1):230-6
16825700
Am J Epidemiol. 1985 Jul;122(1):51-65
4014201
Curr Opin Lipidol. 2008 Apr;19(2):113-21
18388690
Eur Heart J. 2007 Dec;28(23):2937-43
17925342
Nature. 2009 May 21;459(7245):340-2
19458707
Science. 2007 May 11;316(5826):889-94
17434869
Exp Clin Endocrinol Diabetes. 2009 Apr;117(4):194-7
19053021
Obes Rev. 2008 May;9(3):246-50
18373508
Diabetologia. 2009 Jul;52(7):1334-8
19373445
N Engl J Med. 1992 Dec 31;327(27):1893-8
1454084
J Clin Endocrinol Metab. 2009 Apr;94(4):1281-7
19158205
JAMA. 2004 Sep 8;292(10):1188-94
15353531