Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference.

Kateryna Shebanits,Lena M S Carlsson,Ingrid Larsson,Johanna C Andersson-Assarsson,Dan Larhammar,Lars Feuk,Cheng Hu

doi:10.1371/journal.pone.0194668

Abstract

Multiple genetic studies have linked copy number variation (CNV) in different genes to body mass index (BMI) and obesity. A CNV on chromosome 10q11.22 has been associated with body weight. This CNV region spans NPY4R, the gene encoding the pancreatic polypeptide receptor Y4, which has been described as a satiety-stimulating receptor. We have investigated CNV of the NPY4R gene and analysed its relationship to BMI, waist circumference and self-reported dietary intake from 558 individuals (216 men and 342 women) representing a wide BMI range. The copy number for NPY4R ranged from 2 to 8 copies (average 4.6±0.8). Rather than the expected negative correlation, we observed a positive correlation between NPY4R copy number and BMI as well as waist circumference (r = 0.267, p = 2.65×10−7 and r = 0.256, p = 8×10−7, respectively). Each additional copy of NPY4R correlated with 2.6 kg/m2 increase in BMI and 5.67 cm increase in waist circumference (p = 3.3×10−7 and p = 1×10−6, respectively) for women. For men, there was no statistically significant correlation between CNV and BMI. Our results suggest that NPY4R genetic variation influences body weight in women, but the exact role of this receptor appears to be more complex than previously proposed.

Highlights

Excessive weight gain has become one of the major health problems worldwide
Droplet digital PCR analysis demonstrated that NPY4R gene copy number varied from 2 to 8 (2.10–7.51 in men and 2.35–7.95 in women) with 4 being most common in body mass index (BMI) 25.0 kg/ m2
In men and women combined, a positive correlation between NPY4R copy number and BMI was found (r = 0.206, p = 4.85×10−7). It was found in women only (r = 0.267, p = 2.65×10−7) (Fig 1), whereas no statistically significant correlation between NPY4R copy number and BMI was found in men (r = 0.098, p = 0.075)

Summary

Introduction

According to a report from 2013, 37% of men and 38% of women had overweight or obesity [1]. Increased body mass index (BMI) is associated with increased mortality from cardiovascular disease, type 2-diabetes and several types of cancer [2]. Increased waist circumference (WC) is associated with abdominal obesity and increased risk for metabolic complications [3]. Heritability of BMI ranges between 24–80% in family studies and 47–90% in twin studies (for review see[4]). Multiple studies have demonstrated that structural differences in the genome, such as copy number variation (CNV), are associated with variation in BMI [5] and obesity [6,7]

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Discussion

Conclusion