REVIEW
Geneelifestyle interaction on risk
of type 2 diabetes
Paul W. Franks, Jose-Luis Mesa, Anne Helen Harding,
Nicholas J. Wareham
*
Medical Research Council Epidemiology Unit, Elsie Widdowson Laboratories, 120 Fulbourn Road,
Cambridge, CB1 9NL, UK
Received 24 March 2006; received in revised form 4 April 2006; accepted 9 April 2006
KEYWORDS
Geneelifestyle
interaction;
Diabetes
Abstract: The descriptive epidemiology of type 2 diabetes suggests that genee
lifestyle interactions are critical to the development of the condition. However,
unravelling the molecular detail of these interactions is a complex task. The
existing literature is based on small intervention studies or cross-sectional obser-
vational quantitative trait studies. Our systematic review of the literature identi-
fied some evidence of interactions, most notably for a common variant in the
PPAR-gamma gene which appears to interact with the nature of dietary fat
intake. Other interactions have been reported for adrenoceptors, uncoupling pro-
teins, fatty acid binding proteins, apolipoproteins and lipoprotein lipase. There
are, to date, no reports based on the ideal study design which is a case-control
study nested within a cohort. To limit the likelihood of false discovery, such stud-
ies would need to be large and the search for interaction should be restricted to
a priori biologically driven hypotheses. Additional study designs that examine dif-
ferential response to lifestyle change or test interaction in the context of quan-
titative trait studies would complement the nested case-control approach, but
the emphasis here should be on precision of measurement of both phenotype
and lifestyle behaviour.
ª 2006 Elsevier B.V. All rights reserved.
Introduction
The descriptive epidemiology of type 2 diabetes
and its pattern of inheritance provide strong
evidence that the disorder originates from an
interaction between genetic and lifestyle risk
factors [1]. It is not the intention of this article
* Corresponding author. Tel.: þ44 1223 330315; fax: þ44 1223
330316.
E-mail address: nick.wareham@mrc-epid.cam.ac.uk (N.J.
Wareham).
0939-4753/$ - see front matter ª 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.numecd.2006.04.001
Nutrition, Metabolism & Cardiovascular Diseases (2007) 17, 104e124
www.elsevier.com/locate/nmcd