title: A possible genetic link between MTHFR genotype and smoking behavior.
abstract: BACKGROUND
  Hyperhomocysteinemia is an independent risk factor for stroke and other vascular events. The variant methylenetetrahydrofolate reductase (MTHFR) C677T is associated with elevated homocysteine levels, cardiovascular disease and stroke, which supports a causal relationship between hyperhomocysteinemia and vascular disease. However, MTHFR variants have also been reported to be associated with smoking behavior, which could be an important confounder.
  
  
  RESULTS
  We analyzed the MTHFR variants C677T and A1298C in two independent samples of 525 and 535 individuals, respectively. 21% of the non-smokers, but only 12% of the smokers were homozygous carriers of both MTHFR wildtype alleles, i.e. 677CC and 1298AA (Chi² = 15.8; p<0.001; binary regression). Plasma homocysteine levels were higher in smokers (13.9±4.1 µmol/L) than in non-smokers (12.6±4.0 µmol/L; F = 11.4; p = 0.001; ANOVA). Smoking MTHFR 677TT individuals had the highest plasma homocysteine levels (16.2±5.2 µmol/L), non-smoking 677CC individuals had the lowest (12.2±13.6 µmol/L).
  
  
  CONCLUSIONS
  In our study samples, MTHFR variants and smoking behaviour were associated with homocysteine plasma levels. In addition, the MTHFR variants were associated with smoking behaviour. Such an association may be a relevant confounder between MTHFR variants, homocysteine plasma levels and vascular diseases.
authors.affiliation: Department of Neurology, University Hospital Bonn, Bonn, Germany. michael.linnebank@usz.ch
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
authors.forename: Susanna
authors.initials: S
authors.lastname: Moskau
authors.forename: Alexander
authors.initials: A
authors.lastname: Semmler
authors.forename: Barbara
authors.initials: B
authors.lastname: Hoefgen
authors.forename: Gisela
authors.initials: G
authors.lastname: Bopp
authors.forename: Ulf
authors.initials: U
authors.lastname: Kallweit
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Christian G
authors.initials: CG
authors.lastname: Schütz
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000453:epidemiology / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*
chemical_list: D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)