title: Genetic variant screening of MC3R and MC4R genes in early-onset obese children and their relatives among a Thai population: family-based study.
abstract: MC3R (melanocortin-3 receptor) and MC4R (melanocortin-4 receptor) play important roles in energy homeostasis. Severe early-onset obesity, known as monogenic obesity when it is the consequence of a mutation in a single-gene product, may result when energy homeostasis is disrupted. The purpose of our study was to screen for variations of the MC3R and MC4R genes and observe the mode of inheritance of variations in affected families. We used polymerase chain reaction and direct sequencing to analyze the 11 early-onset obese children (probands) with their 71 family members, together with DNA from 100 healthy subjects used as controls. No novel mutations were found in the MC3R gene. Two previously described polymorphisms, rs3746619 and rs3827103, were detected in the MC3R gene. It was not associated with any obesity-related phenotypes. Three heterozygous variations of the MC4R gene were detected in 3 of 11 probands. The rs34114122 and rs61741819 variations have previously been reported, but rs182455344 was novel. Moreover, each MC4R variant was also found in a number of family members, indicating that this molecular analysis of a family-based study showed an autosomal dominant pattern. Our study indicated that MC4R variations in early-onset obese Thai children were found, and transmission of these variations in each family is in the dominant pattern. These variants could possibly contribute to a genetic influence of early-onset obesity in Thais. There is no evidence of any association between MC3R variations and obesity.
authors.affiliation: Department of Tropical Nutrition & Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Wannaiampikul
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: B
authors.initials: B
authors.lastname: Phonrat
authors.affiliation: Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Tungtrongchitr
authors.affiliation: Division of Molecular Genetics, Department of Research & Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: C
authors.initials: C
authors.lastname: Limwongse
authors.affiliation: Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Chongviriyaphan
authors.affiliation: Division of Endocrinology & Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: J
authors.initials: J
authors.lastname: Santiprabhob
authors.affiliation: Department of Tropical Nutrition & Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: R
authors.initials: R
authors.lastname: Tungtrongchitr
mesh_terms: D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D005828:Genetics, Population; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D013785:Thailand
chemical_list: C505392:MC3R protein, human; C470072:MC4R protein, human; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4