Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #209231
Title: APOA5 gene variation modulates the effects of dietary fat intake on body mass index and obesity risk in the Framingham Heart Study

Author
item CORELLA, DOLORES - UNIV. OF VALENCIA, SPAIN
item Lai, Chao Qiang
item DEMISSIE, SERKALEM - BOSTON UNIVERSITY
item CUPPLES, ADRIENNE - BOSTON UNIVERSITY
item MANNING, ALISA - BOSTON UNIVERSITY
item Tucker, Katherine
item Ordovas, Jose

Submitted to: Journal of Molecular Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/29/2006
Publication Date: 1/9/2007
Citation: Corella, D., Lai, C., Demissie, S., Cupples, A., Manning, A.K., Tucker, K., Ordovas, J.M. 2007. APOA5 gene variation modulates the effects of dietary fat intake on body mass index and obesity risk in the Framingham Heart Study. Journal of Molecular Medicine.85:119-128.

Interpretive Summary: Obesity has been identified "one of today’s most blatantly visible – yet most neglected – public health problems." This rising epidemic of overweight and obesity has been called by some as "globesity" to clearly reflect that is a global problem and that, unless action is taken, billions will suffer from debilitating conditions associated with this disorder. Overeating and sedentary lifestyle are major environmental factors determining the current globesity; however, genetic factors are also important to predispose some people to obesity. However, the relationship between obesity and its health consequences (diabetes, cardiovascular disease) may be also determine by genetic factors. In this research we have examined the relation between common mutations at the APOLIPOPROTEIN A5 (APOA5) gene (that we have previously shown to be associated with blood triglyceride levels, a risk factor for heart disease), and macronutrient intake (total fat, carbohydrate and protein) in their relation to body mass index (BMI) and obesity risk in 1073 men and 1207 women participating in the Framingham Offspring Study. We found a consistent and statistically significant interaction between one of the polymorphisms known as –1131T>C SNP and total fat intake for BMI. This interaction was dose-dependent. In subjects homozygous for the –1131T major allele, BMI increased as total fat intake increased. Conversely, this increase was not present in carriers of the –1131C minor allele. In conclusion, the APOA5 –1131T>C SNP, which is present in 13% of this population, modulates the effect of fat intake on BMI and obesity risk in both men and women.

Technical Abstract: Diet is an important environmental factor interacting with our genes to modulate the likelihood of developing lipid disorders and consequently cardiovascular disease risk. Our objective was to study whether dietary intake modulates the association between APOA5 gene variation and body weight in a large population-based study. Specifically, we have examined the interaction between the APOA5 –1131T>C and 56C>G (S19W) polymorphisms and macronutrient intake (total fat, carbohydrate and protein) in their relation to body mass index (BMI) and obesity risk in 1073 men and 1207 women participating in the Framingham Offspring Study. We found a consistent and statistically significant interaction between the –1131T>C SNP (but not the 56C>G) and total fat intake for BMI. This interaction was dose-dependent and no statistically significant heterogeneity by gender was detected. In subjects homozygous for the –1131T major allele, BMI increased as total fat intake increased. Conversely, this increase was not present in carriers of the –1131C minor allele. Accordingly, we found significant interactions in determining obesity and overweight risks. APOA5–1131C minor allele carriers had a lower obesity risk (OR:0.61, 95% CI:0.39-0.98; P=0.032) and overweight risk (OR:0.63; 95% CI:0.41-0.96: P=0.031) compared with TT subjects in the high fat intake group (>= 30% of energy ) but not when fat intake was low (OR: 1.16, 95%CI: 0.77-1.74; P=0.47 and OR=1.15, 95%CI: 0.77-1.71; P=0.48) for obesity and overweight respectively). When specific fatty acid groups were analyzed, monounsaturated fatty acids showed the highest statistical significance for these interactions. In conclusion, the APOA5 –1131T>C SNP, which is present in 13% of this population, modulates the effect of fat intake on BMI and obesity risk in both men and women.