The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition:a fMRI study

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypegender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning.

The COMT Va

Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription.</p> <p>Methods</p> <p>In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins.</p> <p>Results</p> <p>Here, we have shown that the high enzymatic activity genotype of CCND1^High(AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0–1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01–1.84)]. The heterozygous COMT^Medium(MetVal) and the high enzymatic activity of COMT^High(ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07–1.68)] and [OR: 1.4, 95%CI (1.07–1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMT^High(ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73–1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: <b>2.22</b>, 95%CI (1.49–3.28)] and Finland [OR: <b>1.73</b>, 95%CI (1.08–2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity.</p> <p>Conclusion</p> <p>Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.</p

COMT val158met influence on electroconvulsive therapy response in major depression

There is strong evidence for a genetic contribution to the pathogenesis of depression, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, the effect of COMT val158met on response to electroconvulsive therapy (ECT) was analyzed in a sample of 104 Caucasian patients (f = 71, m = 33) with pharmacologically treatment-resistant Major Depression. The higher active COMT 158val allele was found to be associated with (1) higher pre-ECT severity of depression and (2) better treatment response to ECT particularly regarding the core symptoms of depression as well as sleep-related symptoms. These findings were restricted to the female subgroup of patients. In summary, the present study supports a potentially gender-specific significant impact of COMT gene variation on electroconvulsive therapy response, with COMT 158val risk allele carriers suffering from more severe, pharmacologically less efficiently treatable depression and thus possibly deriving greater benefit from ECT in the first place.Katharina Domschke, Maxim Zavorotnyy, Julia Diemer, Sarina Nitsche, Christa Hohoff, Bernhard T. Baune, Juergen Deckert, Volker Arolt and Peter Zwanzge