Purpose: Resilience refers to the individual positive capacity to cope with stress and to restore homeostasis, which may be mediated by adaptive neurobiological changes in the brain. We investigated the genetic influence of the catechol-O-methyltransferase (COMT) Val158Met and the brain-derived neurotrophic factor (BDNF) Val66Met for individual differences in resilience in healthy Korean college students. Methods: A sample of 321 healthy college volunteers (167 males, 154 females) was assessed by genotyping and with the 25-item Connor-Davidson Resilience Scale. Two-way analysis of covariance was used to test the association between participants' COMT and BDNF functional polymorphisms and their resilience. Results: A significant main effect of the COMT polymorphism on resilience and a gene-gene interaction effect between the COMT and BDNF on resilience were observed for males. Male subjects with the COMT Met-present genotype had a significantly higher resilience than those with the Val/Val genotype. Among males with the COMT Val/Val genotype, subjects with the homozygous Val allele of the BDNF tended to have lower resilience than the BDNF Met carriers, while among males with the COMT Met-present genotype, those with the homozygous Val allele of the BDNF tended to have higher resilience than BDNF Met carriers. No main or interaction effects of the COMT and BDNF on resilience were observed for females. Conclusion: These findings suggest the effects of COMT Val158Met polymorphism on resilience could be modulated by BDNF Val66Met polymorphism in males.

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