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Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers.

Halldén, Sara LU ; Sjögren, Marketa LU ; Hedblad, Bo LU ; Engström, Gunnar LU ; Narkiewicz, Krzysztof ; Hoffmann, Michal ; Wahlstrand, Björn ; Hedner, Thomas and Melander, Olle LU orcid (2013) In Heart 99(13). p.949-953
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 Malmö Diet and Cancer Study (MDCS), a population based prospective cohort... (More)
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 Malmö 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. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Heart
volume
99
issue
13
pages
949 - 953
publisher
BMJ Publishing Group
external identifiers
  • wos:000319915100012
  • pmid:23624487
  • scopus:84878793425
  • pmid:23624487
ISSN
1355-6037
DOI
10.1136/heartjnl-2013-303634
language
English
LU publication?
yes
id
0ab93e84-30da-459f-b92b-ea29286b4392 (old id 3733281)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23624487?dopt=Abstract
date added to LUP
2016-04-01 10:18:20
date last changed
2024-01-06 13:23:53
@article{0ab93e84-30da-459f-b92b-ea29286b4392,
  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 Malmö 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&lt;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.}},
  author       = {{Halldén, Sara and Sjögren, Marketa and Hedblad, Bo and Engström, Gunnar and Narkiewicz, Krzysztof and Hoffmann, Michal and Wahlstrand, Björn and Hedner, Thomas and Melander, Olle}},
  issn         = {{1355-6037}},
  language     = {{eng}},
  number       = {{13}},
  pages        = {{949--953}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Heart}},
  title        = {{Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers.}},
  url          = {{https://lup.lub.lu.se/search/files/1732021/4092026.pdf}},
  doi          = {{10.1136/heartjnl-2013-303634}},
  volume       = {{99}},
  year         = {{2013}},
}