title: Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  The Malmö Diet and Cancer Study (MDCS), a population based prospective cohort study (n=30 447).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Clinical Sciences, Lund University, Clinical Research Center, Entrance 72, Building 91, Floor 12, Malmö University Hospital, Malmö SE 205 02, Sweden. sara.hallden@med.lu.se
authors.forename: Sara
authors.initials: S
authors.lastname: Halldén
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Narkiewicz
authors.forename: Michal
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Björn
authors.initials: B
authors.lastname: Wahlstrand
authors.forename: Thomas
authors.initials: T
authors.lastname: Hedner
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000401:mortality; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics* / Q000401:mortality; D016540:Smoking Cessation; D000074606:Smoking Prevention; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human