BackgroundSuicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.MethodsWe genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.ResultsThere were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.ConclusionsThe study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.
LASS1 is the mammalian homologue of yeast longevity-assurance gene 1 (LAG1) which is differentially expressed during the yeast replicative life span and was shown to play a role in determining yeast longevity. Growth/differentiation factor 1 (GDF1) is a transforming growth factor-beta family member that was originally isolated from an mouse embryo cDNA library. GDF1 is expressed specifically in the nervous system and functions in left-right patterning of the mouse embryo. To explore the potential role of LASS1 in rat neuron aging, northern blot analysis for LASS1 mRNA was performed and detected a 2.7 kb transcript in adult rat cerebral cortex. Cloning and sequence analysis revealed that this transcript contains two nonoverlapping open reading frames (ORFs), LASS1 and GDF1, which are quite different to the predicted sequences in GenBank (accession number XM_224734 and XM_224733). The alignment with the rat genome database revealed this transcript matches the sequence of rat chromosome 16 genomic contig (GenBank accession number NW_047470) between nucleotide positions 1935060th and 1919439th, which contains eight exons and seven introns. Multiple sequence analysis revealed high conservation of the two ORFs. The phylogenetic analysis showed very close evolutionary relationship among rat, mouse and human. It raises the possibility that this mRNA may give rise to two different proteins and the conserved bicistronic structure might be of unknown significance.
Primary cultures of human gastric epithelial cells were tested for induction of unscheduled DNA synthesis (UDS) by sterigmatocystin (ST) and T-2 toxin. Autoradiographic results indicated that ST (10(-6)-10(-4)M) induced UDS in the presence of S9 activation system. The repair rates were 24-91% (net grains > or = 3) and 2-71% (net grains > or = 5). T-2 toxin did not induce UDS in this study.
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