scholarly journals Identification of Slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour

2018 ◽  
Author(s):  
Judit García-González ◽  
Alistair J. Brock ◽  
Matthew O. Parker ◽  
Riva Riley ◽  
David Jolliffe ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Startle Reflex ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Snp Analysis ◽  
Adult Fish ◽  
Genetics Research ◽  
Inactivating Mutations ◽  
Serotonergic Antagonist

ABSTRACTTo facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. Of 30 ENU mutagenized families screened, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations in the families, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants that predict cigarette consumption and likelihood of cessation. Characterisation of slit3 mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased htr1aa mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.

scholarly journals Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Judit García-González ◽  
Alistair J Brock ◽  
Matthew O Parker ◽  
Riva J Riley ◽  
David Joliffe ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Startle Reflex ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Snp Analysis ◽  
Adult Fish ◽  
Genetics Research ◽  
Inactivating Mutations ◽  
Serotonergic Antagonist ◽  
Sibling Groups

To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F3 fish, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of slit3 mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased htr1aa mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.

Smoking behaviour and associated factors of illicit cigarette consumption in a border province of southern Thailand

2011 ◽  
Vol 22 (4) ◽  
pp. 255-260 ◽  
Author(s):  
Chittawet Ketchoo ◽  
Rassamee Sangthong ◽  
Virasakdi Chongsuvivatwong ◽  
Alan Geater ◽  
Edward McNeil
Keyword(s):  
Associated Factors ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Southern Thailand

Impacts of Canada’s minimum age for tobacco sales (MATS) laws on youth smoking behaviour, 2000–2014

2018 ◽  
Vol 27 (e2) ◽  
pp. e105-e111 ◽  
Author(s):  
Russell Clarence Callaghan ◽  
Marcos Sanches ◽  
Jodi Gatley ◽  
James K Cunningham ◽  
Michael Oliver Chaiton ◽  
...  
Keyword(s):  
Smoking Status ◽  
Age Groups ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Institute Of Medicine ◽  
Youth Smoking ◽  
Absolute Increase ◽  
Smoking Intensity ◽  
Tobacco Sales ◽  
Minimum Age

BackgroundRecently, the US Institute of Medicine has proposed that raising the minimum age for tobacco purchasing/sales to 21 years would likely lead to reductions in smoking behavior among young people. Surprisingly few studies, however, have assessed the potential impacts of minimum-age tobacco restrictions on youth smoking.ObjectiveTo estimate the impacts of Canadian minimum age for tobacco sales (MATS) laws on youth smoking behaviour.DesignA regression-discontinuity design, using seven merged cycles of the Canadian Community Health Survey, 2000–2014.ParticipantsSurvey respondents aged 14–22 years (n=98 320).ExposureCurrent Canadian MATS laws are 18 years in Alberta, Saskatchewan, Manitoba, Quebec, the Yukon and Northwest Territories, and 19 years of age in the rest of the country.Main outcomesCurrent, occasional and daily smoking status; smoking frequency and intensity; and average monthly cigarette consumption.ResultsIn comparison to age groups slightly younger than the MATS, those just older had significant and abrupt increases immediately after the MATS in the prevalence of current smokers (absolute increase: 2.71%; 95% CI 0.70% to 4.80%; P=0.009) and daily smokers (absolute increase: 2.43%; 95% CI 0.74% to 4.12%; P=0.005). Average past-month cigarette consumption within age groups increased immediately following the MATS by 18% (95% CI 3% to 39%; P=0.02). There was no evidence of significant increases in smoking intensity for daily or occasional smokers after release from MATS restrictions.ConclusionThe study provides relevant evidence supporting the effectiveness of Canadian MATS laws for limiting smoking among tobacco-restricted youth.

Distinct Haplogenotypes of the Dopamine D2 Receptor Gene are Associated with Non-smoking Behaviour and Daily Cigarette Consumption

2009 ◽  
Vol 42 (02) ◽  
pp. 41-50 ◽  
Author(s):  
C. Wernicke ◽  
J. Reese ◽  
A. Kraschewski ◽  
G. Winterer ◽  
H. Rommelspacher ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
Receptor Gene ◽  
D2 Receptor ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Dopamine D2

Lack of TNFα mRNA expression in cervical cancer is not associated with loss of heterozygosity at 6p21.3, inactivating mutations or promoter methylation

2008 ◽  
Vol 45 (1) ◽  
pp. 152-159 ◽  
Author(s):  
Judith N. Kloth ◽  
Arko Gorter ◽  
Natalja ter Haar ◽  
Willem E. Corver ◽  
Ekaterina S. Jordanova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Mrna Expression ◽  
Loss Of Heterozygosity ◽  
Promoter Methylation ◽  
Inactivating Mutations

CD30 Expression in Diffuse Large B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1558-1558 ◽  
Author(s):  
Graham W. Slack ◽  
Christian Steidl ◽  
Laurie H. Sehn ◽  
Randy D. Gascoyne
Keyword(s):  
B Cell ◽  
Mrna Expression ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Independent Predictor ◽  
B Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
Genetics Research ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1558 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with a variable clinical course. The addition of rituximab (R) to CHOP combination chemotherapy has improved overall (OS) and progression free survival (PFS) but some patients progress despite treatment and alternative therapies are needed. Brentuximab vedotin is an antibody-drug conjugate that targets CD30. It is efficacious in the treatment of relapsed Hodgkin lymphoma and relapsed systemic anaplastic large cell lymphoma, two lymphomas associated with CD30 expression. The association between DLBCL and CD30 expression has not been well described. The aim of this study was to examine CD30 expression in DLBCL. Design: 395 cases of formalin-fixed paraffin-embedded DLBCL (excluding PMBCL) in a tissue microarray were independently evaluated by two pathologists for expression of CD30, CD10, BCL6, and MUM1 by immunohistochemistry (IHC) and EBV RNA (EBER) by in situ hybridization. CD30 expression was correlated with cell of origin (COO) phenotype, OS and PFS, EBV infection, International Prognostic Index (IPI) score and CD30 mRNA expression. The COO phenotype, germinal center B-cell like (GCB) or non-GCB, was determined by IHC using the Hans algorithm. CD30 mRNA expression and COO genotype by gene expression profiling (GEP) were determined using Affymetrix U133 2.0 Plus arrays (n=170). Outcome analysis only included patients treated with R-CHOP chemotherapy. CD30 was considered positive by IHC if any malignant cells exhibited membranous staining. The threshold for calling higher CD30 expression by GEP was determined using X-Tile software. Results: 25% (95/385) of DLBCL cases expressed CD30 by IHC with excellent concordance between two observers (r = 0.94). CD30 expression trended towards a non-GCB phenotype but was not significantly different (p=0.067). CD30 expression was not associated with PFS or OS in all R-CHOP treated cases (n=313); however, it was associated with a prolonged PFS in GCB-DLBCL (n=147) (p=0.019). In GCB-DLBCL CD30 expression remained an independent predictor of PFS in a multivariate analysis with IPI (p=0.038). CD30 expression by IHC was significantly associated with higher levels of CD30 mRNA (p=0.002). ABC-DLBCL exhibited significantly higher expression levels of CD30 mRNA (p=0.037). Higher CD30 mRNA expression was associated with a prolonged PFS in all R-CHOP treated DLBCL (p=0.012) as well as in DLBCL with a GCB-genotype (p=0.008), but not ABC or U-genotypes. Higher CD30 mRNA expression was also associated with a prolonged OS in the GCB-genotype (p=0.022). In the GCB-genotype higher CD30 mRNA expression remained an independent predictor of PFS, but not OS, in a multivariate analysis with IPI (p=0.037). EBV was identified in 3% of DLBCL (11/391), all of which exhibited a non-GCB phenotype (p=0.001) and were almost exclusively positive for CD30 expression (10/11)(p=<0.001). Conclusions: CD30 is expressed in approximately 25% of DLBCL and brentuximab vedotin could be considered for study in combination with traditional front-line therapies or as an alternative therapy in the relapsed or refractory disease. CD30 immunohistochemistry may be useful as a prognostic marker in R-CHOP treated GCB-DLBCL and the significant association of CD30 with EBV-positive non-GCB DLBCL suggests a distinct pathobiology for these cases. Disclosures: Slack: Seattle Genetics: Research Funding. Steidl:Seattle Genetics: Research Funding. Gascoyne:Seattle Genetics: Research Funding.

scholarly journals The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond

2013 ◽  
Vol 20 (4) ◽  
pp. C13-C17 ◽  
Author(s):  
Jenny Welander ◽  
Peter Söderkvist ◽  
Oliver Gimm
Keyword(s):  
Mrna Expression ◽  
Loss Of Heterozygosity ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Mutation Database ◽  
Nf1 Gene ◽  
Inactivating Mutations

Patients suffering from the neurofibromatosis type 1 syndrome, which is caused by germline mutations in the NF1 gene, have a tiny but not negligible risk of developing pheochromocytomas. It is, therefore, of interest that the NF1 gene has recently been revealed to carry somatic, inactivating mutations in a total of 35 (21.7%) of 161 sporadic pheochromocytomas in two independent tumor series. A majority of the tumors in both studies displayed loss of heterozygosity at the NF1 locus and a low NF1 mRNA expression. In view of previous findings that many sporadic pheochromocytomas cluster with neurofibromatosis type 1 syndrome-associated pheochromocytomas instead of forming clusters of their own, NF1 inactivation appears to be an important step in the pathogenesis of a large number of sporadic pheochromocytomas. A literature and public mutation database review has revealed that pheochromocytomas are among those human neoplasms in which somatic NF1 alterations are most frequent.

scholarly journals Nuclear Respiratory Factor-1, a Novel SMAD4 Binding Protein, Represses TGF-β/SMAD4 Signaling by Functioning as a Transcriptional Cofactor

2021 ◽  
Vol 22 (11) ◽  
pp. 5595
Author(s):  
Nirmal Rajasekaran ◽  
Kyoung Song ◽  
Jin-Hee Lee ◽  
Yun Wei ◽  
Özgür Cem Erkin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Homozygous Deletion ◽  
Negative Regulator ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Cancer Types ◽  
Inactivating Mutations

SMAD4, a key regulator of transforming growth factor-β (TGF-β) signaling, plays a major role in cell growth, migration, and apoptosis. In particular, TGF-β/SMAD induces growth arrest, and SMAD4 induces the expression of target genes such as p21WAF1 and p15INK4b through its interaction with several cofactors. Thus, inactivating mutations or the homozygous deletion of SMAD4 could be related to tumorigenesis or malignancy progression. However, in some cancer types, SMAD4 is neither mutated nor deleted. In the current study, we demonstrate that TGF-β signaling with a preserved SMAD4 function can contribute to cancer through associations with negative pathway regulators. We found that nuclear respiratory factor-1 (NRF1) is a novel interaction SMAD4 partner that inhibits TGF-β/SMAD4-induced p15INK4b mRNA expression by binding to SMAD4. Furthermore, we confirmed that NRF1 directly binds to the core region of the SMAD4 promoter, thereby decreasing SMAD4 mRNA expression. On the whole, our data suggest that NRF1 is a negative regulator of SMAD4 and can interfere with TGF-β/SMAD-induced tumor suppression. Our findings provide a novel perception into the molecular basis of TGF-β/SMAD4-signaling suppression in tumorigenesis.

scholarly journals Dutch youth’s smoking behaviour during a partial covid-19 lockdown

2021 ◽  
Author(s):  
Tessa R.D. Van Deelen ◽  
Bas Van den Putte ◽  
Anton E. Kunst ◽  
Mirte A. G. Kuipers
Keyword(s):  
Risk Factor ◽  
The Netherlands ◽  
Smoking Prevalence ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Cross Sectional

Previous research found that adult smokers increased their smoking in response to the Covid-19 lockdown in spring 2020. This study explored changes in youth’s smoking during, compared to before, the partial lockdown in the Netherlands in a cross-sectional sample of 287 adolescents. Smoking prevalence increased from 4.5% to 5.2%. Cigarette consumption remained the same on school days and increased with +1.9 cigarettes per weekend day. The largest increase in cigarette consumption on weekend days was observed for adolescents who 1) did not consider smoking a risk factor for contracting Covid-19 (+4.5), 2) had smoking siblings (+4.1), and 3) had smoking friends (+2.4). Youth without smoking friends (-0.8) and who considered smoking a risk factor for Covid-19 (-0.2) decreased their cigarette consumption.

scholarly journals Exploring the inter-relationship of smoking age-at-onset, cigarette consumption and smoking persistence: genes or environment?

2007 ◽  
Vol 37 (9) ◽  
pp. 1357-1367 ◽  
Author(s):  
KATHERINE I. MORLEY ◽  
MICHAEL T. LYNSKEY ◽  
PAMELA A. F. MADDEN ◽  
SUSAN A. TRELOAR ◽  
ANDREW C. HEATH ◽  
...  
Keyword(s):  
Sex Differences ◽  
Environmental Factors ◽  
Age At Onset ◽  
Smoking Behaviour ◽  
Cigarette Consumption ◽  
Males And Females ◽  
Genetic And Environmental Factors ◽  
Relationship Of ◽  
Modelling Methods ◽  
Insight Into

ABSTRACTBackgroundWe investigated the genetic and environmental contributions to covariation between smoking age-at-onset, cigarette consumption and smoking persistence.MethodMultivariate biometrical modelling methods were applied to questionnaire data from Australian twins and their siblings (14 472 individuals from 6247 families). The contributions of genetic and environmental factors to covariation between the three traits were estimated, allowing for sex differences in both trait prevalence and the magnitude of genetic and environmental effects.ResultsAll traits were moderately heritable in males and females (estimates between 0·40 and 0·62), but there were sex differences in the extent to which additive genetic influences were shared across traits. Twin-specific environmental factors accounted for a substantial proportion of the variance in smoking age-at-onset in females (0·19) and males (0·12), but had little influence (<0·08) on other traits. Unique environmental factors were estimated to have a moderate influence on smoking age-at-onset (0·17 for females, 0·19 for males), but a stronger influence on other traits (between 0·39 and 0·49).ConclusionsThese results provide some insight into observed sex differences in smoking behaviour, and suggest that searching for pleiotropic genes may prove fruitful. However, further work on phenotypic definitions of smoking behaviour, particularly persistence, is warranted.

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