Association between Single Nucleotide Polymorphisms and Weight Reduction in Behavioural Interventions-A Pooled Analysis.

Christina Holzapfel,Susan A Jebb,Johanna Graf-Schindler,Ian D Caterson,Thomas Illig,Hans Hauner,Theresa Drabsch,Sabine Sag,Lynne Stecher,Andrea Baessler,Christina Strack,Marcus Fischer,Harald Grallert

doi:10.3390/nu13030819

Abstract

Knowledge of the association between single nucleotide polymorphisms (SNPs) and weight loss is limited. The aim was to analyse whether selected obesity-associated SNPs within the fat mass and obesity-associated (FTO), transmembrane protein 18 (TMEM18), melanocortin-4 receptor (MC4R), SEC16 homolog B (SEC16B), and brain-derived neurotrophic factor (BDNF) gene are associated with anthropometric changes during behavioural intervention for weight loss. genetic and anthropometric data from 576 individuals with overweight and obesity from four lifestyle interventions were obtained. A genetic predisposition score (GPS) was calculated. Our results show that study participants had a mean age of 48.2 ± 12.6 years and a mean baseline body mass index of 33.9 ± 6.4 kg/m2. Mean weight reduction after 12 months was −7.7 ± 10.9 kg. After 12 months of intervention, the MC4R SNPs rs571312 and rs17782313 were significantly associated with a greater decrease in body weight and BMI (p = 0.012, p = 0.011, respectively). The investigated SNPs within the other four genetic loci showed no statistically significant association with changes in anthropometric parameters. The GPS showed no statistically significant association with weight reduction. In conclusion there was no consistent evidence for statistically significant associations of SNPs with anthropometric changes during a behavioural intervention. It seems that other factors play a more significant in weight management than the investigated SNPs.

Highlights

Obesity remains one of the largest challenges for global health
The calculation of the cumulative effect of risk alleles in five genetic variants within an individual genetic predisposition score (GPS) was not associated with anthropometric changes
Existing literature on the same SNPs or SNPs in high LD to those analysed in this study showed no significant association with weight loss after 6 or 12 months in adults with overweight and obesity: rs6548238 of the transmembrane protein 18 (TMEM18) gene, rs6265 of the brain-derived neurotrophic factor (BDNF) gene, rs10913469, and rs543874 of the

Summary

Introduction

Obesity remains one of the largest challenges for global health. Global obesity prevalence will reach 18% in men and surpass 21% in women by [1]. Medical treatment guidelines suggest a combination of dietary, physical, and behavioural changes of at least 6 to 12 months duration to achieve sustained weight loss [3]. Behavioural interventions are associated with modest mean weight losses after 12 months but there is considerable unexplained inter-individual heterogeneity in outcomes [4]. Heterogeneity may result from differences in adherence to the intervention but may be attributable to the complex mechanisms of body weight regulation and genetic susceptibility. Better knowledge of the determinants of weight loss success is a prerequisite for the improvement of current treatment strategies in terms of personalised care

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Discussion

Conclusion