OBJECTIVETo screen the coding region of melanocortin-4 receptor gene (MC4R) for mutations in children, analyze the association of the identified variants with obesity-related phenotypes, and predict the potential functions of the identified variants.

METHODSA case-control study was conducted in 160 severely obese children and 100 normal-weight controls, all aged 7-18 years. Their anthropometric data were collected and blood tests were performed. The coding region of MC4R gene was screened by polymerase chain reaction (PCR), single strand conformation polymorphism and sequencing, and the potential functions of the identified variants were predicted by related online databases.

RESULTSThree heterozygous missense mutations were identified in obese children (Val95Ile, Val166Ile and Val179Ala), and one heterozygous missense mutation was found in controls (Met218Thr). Val103Ile variant was found to be carried by seven subjects in the obese group and six in the control group (P>0.05). Val179Ala was a newly identified heterozygous mutation. No significant differences in BMI, weight, waist circumstance, hip circumstance, serum lipid parameters, fasting glucose, and body fat percentage were found between Val95Ile, Val166Ile or Val179Ala mutation carriers and non-carriers in obese children. The function prediction of the variants showed that all the five identified variants influenced the protein function.

CONCLUSIONSFive variants were identified in the coding region of MC4R gene, among which Val179Ala was newly identified. All the five variants might influence the protein function as evidenced by online prediction.