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United States Department of Agriculture

Agricultural Research Service

Title: The -256T>C Polymorphism in the Apolipoprotein A-II Gene Promoter Is Associated with Body Mass Index and Food Intake in the Genetics of Lipid Lowering Drugs and Diet Network Study

Authors
item Corella, Dolores - UNIV OF VALENCIA, SPAIN
item Arnett, Donna - UNIV OF ALABAMA
item Tsai, Michael - UNIVERSITY OF MINNESOTA
item Kabagambe, Edmond - UNIV OF ALABAMA
item Peacock, James - UNIVERSITY OF MINNESOTA
item Hixson, James - UNIV OF TEXAS HEALTH CTR
item Straka, Robert - UNIVERSITY OF MINNESOTA
item Province, Michael - WASHINGTON UNIV MED SCH
item LAI, CHAO QIANG
item PARNELL, LAURENCE
item Borecki, Ingrid - WASHINGTON UNIV MED SCH
item Ordovas, Jose

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 29, 2007
Publication Date: June 1, 2007
Citation: Corella, D., Arnett, D.K., Tsai, M.Y., Kabagambe, E.K., Peacock, J.M., Hixson, J.E., Straka, R.J., Province, M., Lai, C., Parnell, L.D., Borecki, I., Ordovas, J.M. 2007. The -256T>C Polymorphism in the Apolipoprotein A-II Gene Promoter Is Associated with Body Mass Index and Food Intake in the Genetics of Lipid Lowering Drugs and Diet Network Study. Clinical Chemistry.53:1144-1152.

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 are 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. Therefore, there is need to explore genetic, dietary, biological, behavioral, and environmental factors influencing the development and consequences of obesity and related disorders across the lifespan. We studied the association between a functional apolipoprotein (APOA2) promoter polymorphism (-265T>C) and plasma lipids (fasting and postprandial), anthropometric variables, and food intake in 514 men and 564 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. We observed that individuals homozygous for the -265C allele had statistically higher body mass index (BMI) than did carriers of the T allele. Consistently, the risk for obesity in CC individuals compared with T allele carriers almost doubled. Interestingly, total energy intake in CC individuals was statistically higher than in T allele carriers. Likewise, total fat and protein intakes were statistically higher in CC individuals, whereas the intake of carbohydrates was lower. Therefore, we found a polymorphism that was consistently associated with food consumption and obesity, suggesting a new role for APOA2 in regulating dietary intake.

Technical Abstract: BACKGROUND: Apolipoprotein A-II (APOA2) plays an ambiguous role in lipid metabolism, obesity, and atherosclerosis. METHODS: We studied the association between a functional APOA2 promoter polymorphism (-265T>C) and plasma lipids (fasting and postprandial), anthropometric variables, and food intake in 514 men and 564 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. We obtained fasting and postprandial (after consuming a high-fat meal) measures. We measured lipoprotein particle concentrations by proton nuclear magnetic resonance spectroscopy and estimated dietary intake by use of a validated questionnaire. RESULTS: We observed recessive effects for this polymorphism that were homogeneous by sex. Individuals homozygous for the -265C allele had statistically higher body mass index (BMI) than did carriers of the T allele. Consistently, after multivariate adjustment, the odds ratio for obesity in CC individuals compared with T allele carriers was 1.70 (95% CI 1.02-2.80, P = 0.039). Interestingly, total energy intake in CC individuals was statistically higher [mean (SE) 9371 (497) vs 8456 (413) kJ/d, P = 0.005] than in T allele carriers. Likewise, total fat and protein intakes (expressed in grams per day) were statistically higher in CC individuals (P = 0.002 and P = 0.005, respectively). After adjustment for energy, percent of carbohydrate intake was statistically lower in CC individuals. These associations remained statistically significant even after adjustment for BMI. We found no associations with fasting lipids and only some associations with HDL subfraction distribution in the postprandial state. CONCLUSIONS: The -265T>C polymorphism is consistently associated with food consumption and obesity, suggesting a new role for APOA2 in regulating dietary intake.

Last Modified: 9/29/2014