Genetic factors and clinical significance of acanthosis nigricans in obese Japanese children and adolescents

Aim: To clarify the clinical significance of acanthosis nigricans ( AN) and the association of gene polymorphisms in the beta 2- and beta 3-adrenergic receptors (B2ADR and B3ADR) in Japanese obese children and adolescents. Methods: Seventy obese subjects ( 56 boys, 14 girls) from 5 to 19 y of age were examined as to clinical features. Genetic analyses were performed in 83 obese subjects ( 61 boys, 22 girls), 2 to 17 y of age. Typing of gene polymorphisms in B2ADR and B3ADR was achieved by polymerase chain reaction (PCR) of genomic DNA and restriction fragment-length polymorphism analysis (PCRRFLP). Results: The group with AN (n = 30) had higher values for percent overweight, BMI, waist circumference, fasting insulin, HOMA-R, leptin and PAI-1 than the AN-negative group (n = 40), but there were no significant differences in age, sex or percent body fat between the two groups. The prevalences of B2ADR Gly16 and B3ADR Arg64 were significantly higher in AN-positive (n = 26) than in AN-negative (n = 57) subjects. In addition, the AN frequency was significantly higher in the group with both Gly16 and Arg64 than in the group with neither of these alleles (55.6% vs 12.5%, p < 0.05). Conclusion: We demonstrate that AN is a useful clinical marker for the severity of obesity associated with a high BMI, and that B2ADR Gly16 and B3ADR Arg64 are associated synergistically with AN in obese children and adolescents.