Research Article

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.

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.