Development of a Genetic Score to Predict an Increase in HDL Cholesterol Concentration After a Dietary Intervention in Adults with Metabolic Syndrome

ABSTRACT Background Dietary intervention (DI) is a primary strategy to attenuate some of the metabolic abnormalities associated with metabolic syndrome (MetS), including low HDL cholesterol. There is no biomarker that can identify individuals who respond to DI by increasing HDL cholesterol. Objective The aim of this study was to assess the predictive power of a genetic predisposition score (GPS) in Mexican adults with MetS to identify HDL cholesterol responders to DI. Methods This study followed a prospective cohort design. Sixty-seven Mexican adults aged 20–60 y (21% men) with BMI ≥25 and ≤39.9 kg/m², who had at least 3 of 5 positive criteria for MetS, were included. Participants consumed a low saturated fat diet for 2.5 mo (<7% energy as saturated fat, <200 mg of cholesterol/d) and reduced their usual diet by ∼440 kcal/d, a reduction in total energy intake of about 25%. Anthropometry and serum biochemical markers, including HDL cholesterol, were measured before and after DI. A multilocus GPS was constructed using previously reported genetic variants associated with response to diet in subjects with MetS. GPS values, designed to predict the response of HDL cholesterol to the DI, were computed for each individual as the sum of the number of effect alleles across 14 SNPs. Results Individuals were dichotomized as high and low GPS according to median GPS (−2.12) and we observed a difference in HDL cholesterol changes on DI of +3 mg/dL (6.3%) in subjects with low GPS, whereas those with high GPS had HDL cholesterol decreases of −3 mg/dL (−7.9%) (P = 0.04). Conclusions Individuals with low GPS showed greater increases in their HDL cholesterol than those with high GPS. Therefore, the GPS can be useful for predicting the HDL cholesterol response to diet.

Abstract 004: Physical Activity, Television Watching and Genetic Predisposition in Relation to Body Mass Index in Women and Men

Background Previous studies on gene-lifestyle interaction and obesity have largely focused on a single locus, the FTO gene, and overall physical activity, while little attention has been given in the association for sedentary activity as indicated by television (TV) watching. We examined the interactions between leisure-time physical activity and TV watching and the genetic predisposition to increased body mass index (BMI). Methods Longitudinal data were obtained from 7740 women and 4564 men from 2 prospective cohorts: the Nurses’ Health Study and Health Professionals Follow-up Study. Data on physical activity and TV watching were collected 2 years prior to assessment of BMI. A genetic predisposition score was calculated on basis of 32 established BMI-predisposing variants. Results Overall, each additional BMI-increasing allele was associated with an increase of 0.13 (SE 0.01) kg/m 2 in BMI. The effect size for BMI in individuals in the highest physical activity quintile was attenuated compared to that in individuals in the lowest physical activity quintile (0.08 [0.02] vs 0.15 [0.02] kg/m 2 ; P for interaction <0.001). In contrast, the genetic effect on BMI was more pronounced in individuals who spent >40 h/wk of TV watching than that in individuals who spent 0-1 h/wk of TV watching (0.34 [0.10] vs 0.08 [0.04] kg/m 2 ; P for interaction =0.001). Each 4 Mets/d increment in physical activity (equivalents to 1h/d of brisk walking) was associated with a 0.06 (95% CI 0.03-0.08) kg/m 2 reduction in BMI (∼46% of the main effect of each additional BMI-increasing allele), while each 2 h/d increment in TV watching was associated with a 0.03 (0.01-0.06) kg/m 2 increase in BMI (∼23% of the main effect). We estimated that the difference in BMI (∼4.0 kg/m 2 , equivalents to 11.6 kg in body weight for a person 1.70 m tall) between individuals with a genetic predisposition score of 13 (minimum) and those with a score of 43(maximum) could be reduced by half (2.1 kg/m 2 , 6.1 kg in weight) by 1 h/d of brisk walking or increased by 25% (5.0 kg/m 2 , 14.5 kg in weight) by 2h/d of TV watching. Conclusions Greater leisure-time physical activity attenuates the genetic predisposition to increased BMI, whereas sedentary lifestyle indicated by prolonged TV watching accentuates the genetic effects on BMI. Our data suggest that both increasing exercise levels and reducing sedentary behaviors, especially TV watching, independently may mitigate the genetic predisposition to increased BMI.