Neuropeptide Y Promoter Polymorphism Modifies Effects of a Weight-Loss Diet on 2-Year Changes of Blood Pressure: the Pounds Lost Trial

摘要

Neuropeptide Y (NPY) is implicated in the regulation of blood pressure (BP) and NPY pathways in the hypothalamus are sensitive to dietary fat. We evaluated the potential effect of a functional variant rs16147 located in the NPY gene promoter region on the association between 2-year diet intervention and change in multiple BP measures in the randomized Pounds Lost Trial. The NPY rs16147 was genotyped in 723 obese adults who were randomly assigned to one of four diets differing in the target percentages of energy derived from fat, protein, and carbohydrate. The changes of four BP phenotypes including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) during 2-year diet intervention were analyzed. In the total participants and participants with hypertension, we observed significant and consistent interactions between rs16147 genotype and dietary fat intake on changes in multiple BP phenotypes at 2 years (all P for interactions< 0.05). The risk allele (C allele) was associated with a greater reduction of BP phenotypes in response to low-fat diet, while an opposite genetic effect was observed in response to high-fat diet. In addition, the C allele was related to greater changes in 4 BP phenotypes in hypertensive compared to non-hypertensive participants. Our data suggest that NPY rs16147 may modulate the association between dietary fat intake and changes in BP phenotypes, and the C allele exerts a long-term beneficial effect on lowering BP in response to low-fat diet in obese and hypertensive subjects.