Interaction between genes and lifestyle factors on obesity.
Obesity originates from a failure of the body-weight control systems, which may be affected by changing environmental influences. Basically, the obesity risk depends on two important mutually-interacting factors: (1) genetic variants (single-nucleotide polymorphisms, haplotypes); (2) exposure to environmental risks (diet, physical activity etc.). Common single-nucleotide polymorphisms at candidate genes for obesity may act as effect modifiers for environmental factors. More than 127 candidate genes for obesity have been reported and there is evidence to support the role of twenty-two genes in at least five different populations. Gene-environment interactions imply that the synergy between genotype and environment deviates from either the additive or multiplicative effect (the underlying model needs to be specified to appraise the nature of the interaction). Unravelling the details of these interactions is a complex task. Emphasis should be placed on the accuracy of the assessment methods for both genotype and lifestyle factors. Appropriate study design (sample size) is crucial in avoiding false positives and ensuring that studies have enough power to detect significant interactions, the ideal design being a nested case-control study within a cohort. A growing number of studies are examining the influence of gene-environmental interactions on obesity in either epidemiological observational or intervention studies. Positive evidence has been obtained for genes involved in adiposity, lipid metabolism or energy regulation such as PPARgamma2 (Pro12Ala), beta-adrenoceptor 2 (Gln27Glu) or uncoupling proteins 1, 2 and 3. Variants on other genes relating to appetite regulation such as melanocortin and leptin receptors have also been investigated. Examples of some recently-identified interactions are discussed.
Marti
Amelia
A
School of Pharmacy, University of Navarra, Pamplona, Spain. amarti@unav.es
Martinez-González
Miguel Angel
MA
Martinez
J Alfredo
JA
D004032:Diet; D002149:Energy Intake; D004734:Energy Metabolism / Q000235:genetics; D015444:Exercise / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008019:Life Style; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic