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- Halldén, Sara
(författare)
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Inherited smoking behaviour and Human Epididymis Protein 4 predict smoking-related morbidity and mortality
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- GENERAL AIM: To investigate prognostic markers identifying smokers with increased risk of smoking-related diseases in the population. BACKGROUND: Gene variance in the BDNF- respectively CHRNA-gene has been implicated in different smoking behaviours and the risk alleles have also demonstrated an additional risk increase of smoking-related diseases. The Human Epididymis Protein 4 (HE4) is a cancer biomarker that is also affected by active smoking. AIMS: To replicate the associations between the genotypes of BDNF and CHRNA with smoking phenotypes and to test if the genotypes predicted events from tobacco-related diseases. To investigate the association between smokers and HE4 and to test if altered HE4 could predict future events of smoking-related mortality and morbidity in the population (Study III) or 90-day mortality (Study IV) in an acute setting.SUBJECTS: Study I and II was based on the prospective, population-based cohort study of Malmö Diet and Cancer Study (MDCS)(n=30 447), and study III, on the sub-study MDC-Cardiovascular cohort (MDC-CC) (n=6102). In paper IV, a population presenting with acute dyspne at the emergency department of Malmö was investigated, ADYS (n= 963).METHODS: Genotyping of the two polymorphisms, rs4923461 (BDNF) and rs1051730 (CHRNA) was performed in MDCS and correlated to smoking behaviour. In all four studies, participants were stratified according to smoking status and Cox proportional hazard models were used to determine the correlations of the polymorphisms or the levels of HE4 to outcomes during follow-up. RESULTS: The associations with smoking behaviour were confirmed for both genotypes. In current smokers, the risk alleles of BDNF and CHRNA significantly predicted all-cause mortality. CHRNA also predicted a higher risk of incident smoking-related diseases. No associations were seen in never smokers. In MDC-CC, HE4-levels were distinctly elevated in current smokers but not in the ADYS-population. In MDC-CC, elevated HE4 predicted all-cause mortality irrespective of smoking status and in ADYS, HE4 strongly predicted 90-day mortality regardless of underlying disease or smoking status.CONCLUSION: Gene variance of BDNF and CHRNA have impact on smoking behaviour and predicts an increased risk of smoking-related complications in smokers. Plasma levels of HE4 predicts mortality in a long- and short-term perspective and may be used as a disease risk marker in smokers and possibly also in non-smokers. In the future, genotype of BDNF and CHRNA polymorphisms and HE4 levels may be helpful in identifying patients with a higher risk of complications.
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- Halldén, Sara, et al.
(författare)
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Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers
- 2013
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 99:13, s. 949-953
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Tidskriftsartikel (refereegranskat)abstract
- Objective The brain derived neurotrophic factor (BDNF) locus has been implicated in psychiatric and substance related disorders. Recent genome-wide association studies (GWAS) have shown strong associations between single nucleotide polymorphisms in BDNF, smoking behaviour and high body mass index (BMI). Our aim was to test whether genetic BDNF variation alters the risk of smoking related morbidity and mortality. Design Cox proportional hazards models were used to relate the BDNF rs4923461(A/G) polymorphisms to all-cause, cancer and cardiovascular mortality and cardiovascular disease (CVD) incidence adjusted for age, sex, BMI, and smoking quantity. Setting The Malmo Diet and Cancer Study (MDCS), a population based prospective cohort study (n=30 447). Patients We obtained complete data on 25 071 subjects, of whom 6507 were current smokers and 18 564 were non-smokers who underwent a baseline examination from 1991-1996. Main outcome measures During a mean follow-up time of 12 years, 1049 deaths (346 cardiovascular deaths and 492 cancer deaths) and 802 incident CVD events occurred among current smokers. Results The major allele (A) of rs4923461 was significantly associated with ever having smoked (p=0.03) and high BMI (p=0.001). The A-allele was associated with risk of all-cause (HR=1.12, 95% CI 1.00 to 1.25; p<0.05) and CVD (HR=1.23, 95% CI 1.01 to 1.49; p=0.04) mortality. There was no significant association between the rs4923461 and cancer mortality or CVD incidence. Conclusions Our data suggest that smoking-and obesity-associated variation of the BDNF gene affects the risk of death, especially due to cardiovascular causes, in smokers. Determination of the BDNF genotype in smokers may guide the need for smoking cessation interventions.
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- Thomas, Richard D., et al.
(författare)
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DESIREE : Physics with cold stored ion beams
- 2015
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Ingår i: DR2013. - : EDP Sciences. ; 84, s. 01004-01004
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Konferensbidrag (refereegranskat)abstract
- Here we will briefly describe the commissioning of the Double ElectroStatic Ion Ring ExpEriment (DESIREE) facility at Stockholm University, Sweden. This device uses purely electrostatic focussing and deflection elements and allows ion beams of opposite charge to be confined under extreme high vacuum and cryogenic conditions in separate rings and then merged over a common straight section. This apparatus allows for studies of interactions between cations and anions at very low and well-defined centre-of-mass energies (down to a few meV) and at very low internal temperatures (down to a few K).
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