OBJECTIVES: The mutations in gene for the melanocortin-4 receptor (MC4R) are the most common etiology factors of monogenic obesity development. Recently, it has been shown that current life style has a significant impact on the phenotype of MC4R mutation carriers - increases the penetrance of the mutations. We aimed to study the impact of the current age on the time of obesity onset among MC4R mutation carriers. METHODS: DNA analysis of the MC4R gene was performed in 268 unrelated Slovak and Moravian obese children and adolescents 18 years and 28 blood relatives >18 years of the probands with a mutation. RESULTS: Three different previously described heterozygous loss of function MC4R mutations (p.Ser19Alafs*34, p.Ser127Leu, and p.Gly181Asp) were found in 3 <18 years probands, 3 adult probands, and 6 adult obese/overweight family relatives. The age of obesity onset in mutation carriers was 1 year in all probands in the children group and 1-35 years (median 11 years) in adults. The age of the obesity onset significantly correlated (R=0.809, p=0.028) with the current age in all of the MC4R mutation carriers. CONCLUSIONS: The age of obesity onset in the present child generation of MC4R mutation carriers is decreasing compared to the age of onset in their parents' generation. This is in agreement with similarly increasing penetrance of obesity in MC4R mutation carriers and it points out to escalation of obesogenic potential of environment.

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