Kivonat:
Introduction: Rumination is a multidimensional trait which is a
proven risk factor in the vulnerability to depression. The aim
to identify the main risk genes for depression in addition to
the gene-environment interactions pointed to the importance of
intermediate phenotypes, like rumination, to improve our
understanding of the biological mechanisms of depression.
Catechol-O-Methyltransferase (COMT) gene is extensively
investigated in depression with contradictory results but its
association with rumination, as an intermediate phenotype in
depression, has not been investigated yet. Methods: In our
study, four tagging SNPs in the COMT gene (rs933271, rs740603,
rs4680, rs4646316) were genotyped in a nonclinical Hungarian
sample (n=939). We investigated the association between the COMT
gene and rumination scores measured by the Ruminative Response
Scale using haplotype trend regression. Results: We found a
significant association between COMT haplotypes and rumination
scores (p=0.013) but no significant association was apparent
between the functional Val158Met polymorphism (rs4680) and
rumination in any genetic model. Discussion: Variations in the
COMT gene exert complex effects on susceptibility to depression
involving intermediate phenotypes, such as rumination and also
impulsivity, as we previously demonstrated. Both rumination and
impulsivity represent maladaptive cognitive styles that can lead
to depressive state by influencing the response to negative life
events and life stressors. In conclusion, our findings provide
evidence that in addition to other genes, COMT also has a
significant role in the development of depression, and
demonstrate that analysing the complex phenotype associations of
genes by haplotype tagging is a powerful method.