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Title: Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asia populations: replication of a gene-saturated fat interaction

item CORELLA, DOLORES - University Of Valencia
item TAI, E-SHYONG - Singapore General Hospital
item SORLI, JOSE V. - University Of Valencia
item CHEW, SU-KIT - Ministry Of Health - Singapore
item COLTELL, OSCAR - University Of Jaume
item SOTOS-PRIETO, MERCEDES - University Of Valencia
item GARCIA-RIOS, ANTONIO - Reina Sofia University
item ESTRUCH, RAMON - University Of Barcelona
item ORDOVAS, JOSE M. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/26/2010
Publication Date: 5/1/2011
Citation: Corella, D., Tai, E., Sorli, J., Chew, S., Coltell, O., Sotos-Prieto, M., Garcia-Rios, A., Estruch, R., Ordovas, J. 2011. Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asia populations: replication of a gene-saturated fat interaction. International Journal of Obesity. 35(5):666-675.

Interpretive Summary: The prevalence of obesity and overweight continues to increase; currently, an estimated 66% of adult Americans fit within these categories. This trend is unprecedented in U.S. history and is an important underlying cause of many related disorders, including cardiovascular disease, Type 2 diabetes and several cancers, as well as escalating health care costs. Reduction of excess weight is difficult to achieve and even harder to sustain, and there is critical need for effective, proven methods for the primary prevention of weight gain. More tailored recommendations should increase the chance of success, but we don’t have the tools to predict the individual risk as well as responses to therapeutic recommendations. Therefore, we have conducted a large study to investigate the role of a functional genetic variant, known as APOA2 -265T>C, in the regulation of food intake and body weight. Three independent populations in the United States were examined: the Framingham Offspring Study (1454 whites), the Genetics of Lipid Lowering Drugs and Diet Network Study (1078 whites), and Boston-Puerto Rican Centers on Population Health and Health Disparities Study (930 Hispanics of Caribbean origin). The results of this study show that people carrying the genetic variant at the APOA2 gene developed obesity only in the presence of a high saturated fat diet. This was true for the three populations and this is the first time that such replication is achieved across populations in research involving gene and diet interactions. This finding will contribute to the identification of individuals susceptible to diet-induced obesity. Moreover, it will guide the implementation of tailored dietary recommendations to specifically quench their increased predisposition to obesity and cardiovascular diseases.

Technical Abstract: Objective: The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2–saturated fat interaction determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations. Methods: Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n 1/4 907 men and women; aged 67 +/- 6 years) and a multiethnic Asian population (n 1/4 2506 Chinese, n 1/4 605 Malays and n 1/4 494 Asian Indians; aged 39 +/- 12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, biochemical, lifestyle and dietary variables were determined. Homeostasis model assessment of insulin resistance was used in Asians. We analyzed gene–diet interactions between the APOA2 - 265T greater than C polymorphism and saturated fat intake (< or > 22 g per day) on anthropometric measures and IR. Results: Frequency of CC (homozygous for the minor allele) subjects differed among populations (1–15%). We confirmed a recessive effect of the APOA2 polymorphism and replicated the APOA2–saturated fat interaction on body weight. In Mediterranean individuals, the CC genotype was associated with a 6.8% greater BMI in those consuming a high (P 1/4 0.018), but not a low (P 1/4 0.316) saturated fat diet. Likewise, the CC genotype was significantly associated with higher obesity prevalence in Chinese and Asian Indians only, with a high-saturated fat intake (P 1/4 0.036). We also found a significant APOA2–saturated fat interaction in determining IR in Chinese and Asian Indians (P 1/4 0.026). Conclusion: The influence of the APOA2 - 265T>C polymorphism on body-weight-related measures was modulated by saturated fat in Mediterranean and Asian populations.