Endocrine

, Volume 44, Issue 2, pp 386–390

Prevalence of rare MC3R variants in obese cases and lean controls

  • Doreen Zegers
  • Sigri Beckers
  • Rik Hendrickx
  • Jasmijn K. Van Camp
  • Kim Van Hoorenbeeck
  • Kristine N. Desager
  • Guy Massa
  • Luc F. Van Gaal
  • Wim Van Hul
Original Article

DOI: 10.1007/s12020-012-9862-1

Cite this article as:
Zegers, D., Beckers, S., Hendrickx, R. et al. Endocrine (2013) 44: 386. doi:10.1007/s12020-012-9862-1

Abstract

The role of mutations in the melanocortin-3 receptor (MC3R) gene, which is implicated in the regulation of energy homeostasis, is still under debate. Animal studies have clearly proven that, together with the melanocortin-4 receptor (MC4R), the MC3R is a critical receptor for melanocortin peptides within the leptin-melanocortin signaling cascade. However, as several mutations have been found in lean individuals and not all mutations seem to cause receptor dysfunction, results from mutation screens in obese humans remain controversial. In the present study, we screened for rare variants in the MC3R gene of obese children and lean controls to assess the prevalence of MC3R mutations in the Belgian population. We screened 249 severely overweight and obese children and adolescents and 239 lean adults for mutations in the coding region of MC3R. Mutation screening was performed by high resolution melting curve analysis and direct sequencing. We identified four non-synonymous coding variations in the obese population, all of which had been reported previously. In addition, we also found four novel rare MC3R variants in the lean control population, suggesting that not all MC3R mutations are disease-causing. Overall, the total prevalence of rare MC3R variants was 1 % in Belgian obese children and adolescents compared to 1.02 % in lean controls. Ultimately, cosegregation studies combined with comprehensive functional analysis is required to determine the potential pathogenic role of rare MC3R variants in causing human obesity.

Keywords

MC3R Obesity Genetics Mutation analysis 

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Doreen Zegers
    • 1
  • Sigri Beckers
    • 1
  • Rik Hendrickx
    • 1
  • Jasmijn K. Van Camp
    • 1
  • Kim Van Hoorenbeeck
    • 3
  • Kristine N. Desager
    • 3
  • Guy Massa
    • 4
  • Luc F. Van Gaal
    • 2
  • Wim Van Hul
    • 1
  1. 1.Department of Medical GeneticsUniversity of Antwerp, Universiteitsplein 1AntwerpBelgium
  2. 2.Department of Endocrinology, Diabetology and Metabolic DiseasesAntwerp University HospitalAntwerpBelgium
  3. 3.Department of PediatricsAntwerp University HospitalAntwerpBelgium
  4. 4.Department of PediatricsJessa HospitalHasseltBelgium

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