Open AccessThe lack of association between angiotensin‐converting enzyme gene insertion/deletion polymorphism and nicotine dependence in multiple sclerosis
Author(s) -
Nadalin Sergej,
BuretićTomljanović Alena,
Lavtar Polona,
Starčević Čizmarević Nada,
Hodžić Alenka,
Sepčić Juraj,
Kapović Miljenko,
Peterlin Borut,
Ristić Smiljana
Publication year - 2017
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.600
Subject(s) - angiotensin converting enzyme , medicine , genotyping , genotype , renin–angiotensin system , nicotine , endocrinology , allele , polymorphism (computer science) , angiotensin ii , blood pressure , genetics , gene , biology
Objective 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 . Patients and Methods Genotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction. Results 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). Conclusion 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.