Genetic Susceptibility, Dietary Protein Intake, and Changes of Blood Pressure: The POUNDS Lost Trial

Abstract

High blood pressure (BP) is closely related to obesity, and weight loss lowers BP. Evidence has shown considerable interpersonal variation of changes in BP among people experiencing weight loss, and such variation might be partly determined by genetic factors. We assessed the changes in systolic and diastolic BP (SBP/DBP) among 692 participants randomly assigned to 1 of 4 diets varying in macronutrient content for 2 years. Two separate polygenic scores (SBP/DBP-PGS derived from 52/50 single nucleotide polymorphisms) were built for each participant based on 66 BP-associated single nucleotide polymorphisms. During a 2-year intervention, participants in the bottom versus upper tertile of SBP/DBP-PGS had a greater decrease in SBP (△SBP at 6, 12, and 24 months: -3.84 versus -1.61, -4.76 versus -2.75, -2.49 versus -1.63; P=0.001) or in DBP (△DBP at 6, 12, and 24 months: -3.09 versus -1.34, -2.69 versus -1.44, -1.82 versus -0.53; P<0.001). We also found gene-diet interaction on changes in SBP from baseline to 24 months (Pinteraction=0.009). Among participants assigned to a high-protein diet, those with a lower SBP-polygenic scores had greater decreases in SBP at months 6 (P=0.018), months 12 (P=0.007), and months 24 (P=0.089); while no significant difference was observed across the SBP-polygenic scores tertile groups among those assigned to an average-protein diet (all P values >0.05). Our data indicate that genetic susceptibility may affect BP changes in response to weight-loss diet interventions, and protein intake may modify the genetic associations with changes in BP. This trial was registered at URL: http://www.clinicaltrials.gov. Unique identifier: NCT00072995.

Keywords: blood pressure; dietary proteins; hypertension; overweight; weight loss.

Figures

Figure 1.. Trajectory of changes in blood pressure response to weight-loss diets according to tertiles of SBP (left) and DBP (right) polygenic score on over 2 years.

PGS, polygenic score. M0-M24 means intervention time point at baseline, 6, 12, and 24 month. T1-T3 represents the tertiles of SBP/DBP polygenic score.

Figure 2.. Changes in SBP by tertiles of SBP polygenic score in the high-protein and the average-protein diet groups at 6 months, 12 months, and 2 years.

PGS, polygenic score. T1-T3 represents the tertiles of SBP/DBP polygenic score.

Figure 3.. Trajectory of changes in BP according to tertiles of the SBP/DBP polygenic score at 6, 12, and 24 months and dietary intervention groups

PGS, polygenic score. M0-M24 means intervention time point at baseline, 6, 12, and 24 month. T1-T3 represents the tertiles of SBP/DBP polygenic score.