Genotype-specific responses to weight loss diets

Polymorphism of neuropeptide Y gene rs16147 modifies the response to a hypocaloric diet on cardiovascular risk biomarkers and adipokines

De Luis et al., JHND Early View


The main genetic variant described in NPY gene is rs16147 (G-399A) and it is located within the promoter region upstream of the gene for neropeptide Y (NPY). We evaluate the effects of the rs16147 NPY gene polymorphism on metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adult obese patients.


A population of 82 obese patients was analysed in an interventional design of one arm. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for combined GA and AA as a group (minor allele group) and GG as second group (major allele group) (dominant model).


In A allele carriers, the mean (SD) decrease in weight was −2.8 (2.2) kg [decrease in non A allele carriers −2.6 (1.1) kg, P > 0.05), body mass index was −1.2 (0.6) kg m−2 [decrease in non A allele carriers −1.1 (0.8) kg m−2P > 0.05], fat mass was −1.7 (1.4) kg [decrease in non A allele carriers −1.9 (1.3) kg, P > 0.05], waist circumference was −5.5 (3.4) cm [decrease in non A allele carriers −3.7 (4.1) cm, P = 0.006], C-reactive protein (CRP) was −0.7 (0.6) mg dL−1 [decrease in non A allele carriers −0.1 (0.3) mg dL−1P = 0.02], insulin was −1.5 (0.4) mUI L−1 [decrease in non A allele carriers −0.8 (2.0) mUI L−1P = 0.001] and homeostasis model assessment-insulin resistance (HOMA-IR) was −0.4 (0.5) [decrease in non A allele carriers −0.2 (0.1), P = 0.005]. interleukin (IL)-6 changes were significant in A allele carriers [−0.7 (0.2) pg mL−1] versus non A allele carriers [−0.1 (0.3) pg mL−1] (P = 0.01).


We found that the rs164147 genotype affected the reduction of waist circumference, HOMA-IR, insulin, CRP and IL-6 levels in response to weight loss diet in obese subjects.

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