Decreased function of the melanocortin-4 receptor (MC4R) was reported to cause late-onset
obesity and insulin resistance in rodents. Thus mutations in the MC4R gene drew strong attention
as a possible cause of obesity and diabetes. We screened for mutations in the MC4R gene in extremely
obese [body mass index (BMI) [ges ] 35 kg/m2] Japanese with diabetes by direct sequencing. A
heterozygous mutation (V103I) was detected in one case (2.0 %), however the frequency was not
significantly different from that in non-obese (BMI [les ] 24 kg/m2) and non-diabetic subjects (2.7 %).
No other mutations were detected. These results suggest that mutations including V103I in the
MC4R gene are not a major cause of obesity or diabetes in Japanese.