Researchers have identified a genetic marker that makes carriers more susceptible to increased body mass index (BMI) and obesity when consuming diets high in saturated fat, according to a report in the Archives of Internal Medicine [2009;169(20):1897-1906].

Participating investigators were associated with Tufts University, Boston University, the University of Valencia, the University of Alabama, Jaume I University (Castellón, Spain), and the National Center for Cardiovascular Investigation in Madrid.

The investigators had previously reported an association between a single nucleotide polymorphism in the gene promoter of a high-density lipoprotein (HDL) apolipoprotein (APOA2), food intake, and obesity risk in non-Hispanic white Americans. The present study aimed to analyze the association between this genetic marker and obesity-related factors in the Framingham Offspring Study, specifically focusing on gene–diet interactions with fat intake. The study also aimed to determine if these gene–diet interactions were similarly found in other American populations included in other studies. The studies included cross-sectional, 20-year follow-up, and case-control analyses.

A total of 3462 individuals were recruited for participation from the Framingham Offspring Study (n=1454 whites), the Genetics of Lipid Lowering Drugs and Diet Network Study (n=1078 whites), and the Boston–Puerto Rican Centers on Population Health and Health Disparities Study (n=930 Hispanics of Caribbean origin).

In all of the populations, individuals underwent standard assessments to determine height, weight, and waist circumference, as well as fasting glucose, triglycerides, total cholesterol, and HDL cholesterol. Genetic analyses were performed to determine individuals’ APOA2-265T>C genotype. Participants in all study populations completed validated questionnaires to determine dietary intake.

The investigators reported that the prevalence of the genotype of interest (the CC genotype of APOA2 -265T>C) ranged from 10.5% to 16.2%. There was a statistically significant interaction between having the CC genotype of APOA2 and saturated fat intake, when the populations were stratified by BMI. In carriers of the CC genotype, the investigators found a mean increase in BMI of 6.2% (P=.01) between those with high saturated fat intake (≥22 g/day) and those with low saturated fat intake. The genotype was also associated with a significantly higher rate of obesity in all of the populations studied, but only among those with high saturated fat intake.

The study authors noted that previous reports of the association between the CC genotype and BMI had now been extended to a wider population, including Hispanics of Caribbean origin living in Boston. They explained that the findings from this analysis therefore strengthened the concept that regardless of population, individuals with the CC genotype are more susceptible to overweight and obesity when consuming a diet high in saturated fat.

Study limitations discussed by the authors included the assumption that saturated fat intake remained similar over the 20-year follow-up analysis of the Framingham Offspring Study. However, the authors noted that participants of the Framingham Offspring Study have reported stable dietary habits over time, especially with regard to saturated fat intake.

The authors explained that the relationship between saturated fat intake, BMI, and obesity has been controversial, and concluded that this relationship is highly dependent on individuals’ APOA2 -265T>C genotype. They hypothesized that other genes could exhibit similar gene–diet interactions, which may explain the “diversity and complexity” of obesity. With a variety of diets under evaluation for weight loss, including low-fat, low-carbohydrate, and Mediterranean, they emphasized the need for further research into gene–diet interactions to identify which dietary strategies may be most effective in specific individuals.—Kristina Woodworth