Association of the RORA Gene Polymorphism and Seasonal Variations in Mood and Behavior / 수면정신생리

OBJECTIVES: Several evidence has been suggested that the circadian gene variants contribute to the pathogenesis of seasonal affective disorder. In this study, we aimed to investigate the polymorphism in RORA (Retinoid-related orphan receptor A) gene in relation to seasonal variations among healthy young adults in Seoul, Korea. METHODS: A total of 507 young healthy adult subjects were recruited by advertisement. Seasonal variations were assessed by the Seasonality Pattern Assessment Questionnaire (SPAQ). Single-nucleotide polymorphism in the RORA rs11071547 gene was genotyped by PCR in 507 individuals. Considering summer type as confounding factor, we conducted analysis 478 subjects except 29 subjects of summer type. The Chi-square test was conducted to compare differences between groups of seasonals and non-seasonals. Association between genotypes and Global Seasonality Score (GSS) were tested using ANCOVA (Analysis of covariance). RESULTS: In this sample, the prevalence of SAD was 12.1% (winter type 9.3%, summer type 2.8%). There is no significant difference in genotyping distribution of RORA rs11071547 between groups of seasonals and non-seasonals. Global seasonality score (GSS) and scores of all subscales except body weight and appetite were not significantly different between the group with C allele homozygote and the group with T allele homozygote and heterozygote (p-value 0.138). Scores of body weight and appetite were significantly higher in group with C allele homozygotes. CONCLUSION: These results suggest that RORA gene polymorphism play a role in seasonal variations in appetite and body weight and is associated with susceptibility to seasonal affective disorder in some degree in the population studied.

Effects of Cardiotrophin-1 on Adriamycin-Induced Apoptosis in H9c2 Cardiomyoblasts

BACKGROUND AND OBJECTIVES: Adriamycin (doxorubicin, ADR) is a highly effective anti-neoplastic drug, but its clinical use is limited by its adverse side effects on the heart. Cardiotrophin (CT-1), a potent cardiac survival factor, is capable of inhibiting apoptosis in cardiac myocytes. The aim of this study was to investigate the cyto-protective effects of CT-1 against ADR-induced apoptosis in vitro. MATERIALS AND METHODS: We determined a reasonable ADR concentration for inducing cell death by utilizing a cell survival test performed in a dose-dependent manner. To determine the requirements for apoptosis in ADR-treated cardiac myocytes (H9c2 cells), we examined the effect of CT-1 on survival and apoptotic changes using a cell counting kit (CCK), RT-PCR, and Western blotting. RESULTS: In analyzing cell survival as determined by CCK, ADR-induced cell death was found to occur in a dose-dependent manner (50% death at 24 hours after 2 micrometer of ADR), and ADR was shown to decrease procaspase-3. On RT-PCR, expression of Bax-alpha mRNA increased and Bcl-2 decreased during the 24 hours after ADR treatment. Consequently, the ratio of Bax-alpha/Bcl-2 mRNA peaked at 24 hours after ADR treatment. In contrast, CT-1 effectively attenuated the ADR-induced cell death in a dose-dependent manner. The changes in Bax-alpha and Bcl-2 mRNA expression after ADR treatment were reversed by CT-1 (1 ng/mL) treatment. The protein levels of procaspase-3 decreased after ADR treatment, an effect which was reversed by CT-1 treatment. Akt phosphorylation was also increased by CT-1, demonstrating that CT-1 inhibited apoptosis induced by ADR. CONCLUSION: These data demonstrated that ADR-induced apoptosis of cardiomyocytes can be prevented by CT-1; therefore, it may be possible to use CT-1 as a cardioprotective agent during ADR chemotherapy in patients with cancer.