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Variation at the Melanocortin 4 Receptor Gene and Response to Weight-Loss Interventions in the Diabetes Prevention Program

Pan, Qing ; Delahanty, Linda M. ; Jablonski, Kathleen A. ; Knowler, William C. ; Kahn, Steven E. ; Florez, Jose C. and Franks, Paul LU (2013) In Obesity 21(9). p.520-526
Abstract
Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment. Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to... (More)
Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment. Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all P-interaction < 0.05). Conclusion: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Obesity
volume
21
issue
9
pages
520 - 526
publisher
Nature Publishing Group
external identifiers
  • wos:000325426600026
  • scopus:84884907373
  • pmid:23512951
ISSN
1930-739X
DOI
10.1002/oby.20459
language
English
LU publication?
yes
id
3d00f2c7-bdfb-4abe-a541-1c9353de6fcd (old id 4170482)
date added to LUP
2016-04-01 10:05:18
date last changed
2022-04-27 18:19:46
@article{3d00f2c7-bdfb-4abe-a541-1c9353de6fcd,
  abstract     = {{Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment. Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all P-interaction &lt; 0.05). Conclusion: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.}},
  author       = {{Pan, Qing and Delahanty, Linda M. and Jablonski, Kathleen A. and Knowler, William C. and Kahn, Steven E. and Florez, Jose C. and Franks, Paul}},
  issn         = {{1930-739X}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{520--526}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Obesity}},
  title        = {{Variation at the Melanocortin 4 Receptor Gene and Response to Weight-Loss Interventions in the Diabetes Prevention Program}},
  url          = {{http://dx.doi.org/10.1002/oby.20459}},
  doi          = {{10.1002/oby.20459}},
  volume       = {{21}},
  year         = {{2013}},
}