title: The lack of association between angiotensin-converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis.
abstract: Blood-borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE-I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE-I/D polymorphism might influence smoking behavior among patients with MS.
  
  
  
  Genotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction.
  
  
  
  We revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE-I/D polymorphism and either pack-year smoking history or number of cigarettes smoked daily (p>.05, respectively).
  
  
  
  The ACE-I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE-I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.
authors.affiliation: Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia.
authors.forename: Sergej
authors.initials: S
authors.lastname: Nadalin
authors.affiliation: Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia.
authors.forename: Alena
authors.initials: A
authors.lastname: Buretić-Tomljanović
authors.affiliation: Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia.
authors.forename: Polona
authors.initials: P
authors.lastname: Lavtar
authors.affiliation: Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Starčević Čizmarević
authors.affiliation: Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia.
authors.forename: Alenka
authors.initials: A
authors.lastname: Hodžić
authors.affiliation: Postgraduate Studies School of Medicine University of Rijeka Rijeka Croatia.
authors.forename: Juraj
authors.initials: J
authors.lastname: Sepčić
authors.affiliation: Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia.
authors.forename: Miljenko
authors.initials: M
authors.lastname: Kapović
authors.affiliation: Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia.
authors.forename: Borut
authors.initials: B
authors.lastname: Peterlin
authors.affiliation: Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia.
authors.forename: Smiljana
authors.initials: S
authors.lastname: Ristić
mesh_terms: D000328:Adult; D015897:Comorbidity; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics*
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin‐converting enzyme gene; multiple sclerosis; smoking