{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:04:46Z","timestamp":1753862686943,"version":"3.41.2"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Rijeka","award":["13.06.1.1.10"],"award-info":[{"award-number":["13.06.1.1.10"]}]},{"name":"National Research Agency of the Republic of Slovenia","award":["J3-3628"],"award-info":[{"award-number":["J3-3628"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Blood\u2010borne angiotensin<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>is generated from angiotensinogen via cleavage by renin and angiotensin\u2010converting enzyme (<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>), an enzymatic cascade known as the renin\u2013angiotensin system (<jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>). Several lines of evidence indicate that<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>, 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<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>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<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>activity in cerebrospinal fluid and serum among<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>patients. Furthermore, in our previous work with<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>patients from Croatian and Slovenian populations, we demonstrated that the<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010I\/D polymorphism contributes to an elevated<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>risk among male patients. Here we investigated whether the<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010I\/D polymorphism might influence smoking behavior among patients with<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Genotyping was performed in 521 patients (males\/females: 139\/382) using polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We revealed no significant differences in<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>genotype and allele frequencies between smokers and nonsmokers and no significant association between the<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010I\/D polymorphism and either pack\u2010year smoking history or number of cigarettes smoked daily (<jats:italic>p\u00a0<\/jats:italic>&gt;<jats:italic>\u00a0<\/jats:italic>.05, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010I\/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>patients. In the context of reports on the<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010I\/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<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>compared to depression, although not compared to a healthy population. In addition to angiotensin<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, other potential<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>), may deserve study in future.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.600","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T19:14:46Z","timestamp":1479150886000},"source":"Crossref","is-referenced-by-count":1,"title":["The lack of association between angiotensin\u2010converting enzyme gene insertion\/deletion polymorphism and nicotine dependence in multiple sclerosis"],"prefix":"10.1002","volume":"7","author":[{"given":"Sergej","family":"Nadalin","sequence":"first","affiliation":[{"name":"Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Bureti\u0107\u2010Tomljanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polona","family":"Lavtar","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada","family":"Star\u010devi\u0107 \u010cizmarevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alenka","family":"Hod\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juraj","family":"Sep\u010di\u0107","sequence":"additional","affiliation":[{"name":"Postgraduate Studies School of Medicine University of Rijeka Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miljenko","family":"Kapovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borut","family":"Peterlin","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical Genetics University Medical Centre Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smiljana","family":"Risti\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics School of Medicine University of Rijeka Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acmx.2014.12.005"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v69n1219c"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30231"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300997"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0031-6997(24)01509-6","article-title":"Neurotensin and dopamine interactions","volume":"53","author":"Binder E. B.","year":"2001","journal-title":"Pharmacological Reviews"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.12.093"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1997.00550200068012"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2015.03.006"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.05.013"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282X20140159"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0628-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.122"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.17.2060"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.01.020"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365510410002760"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00494-4"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-1376-0_10"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68031304.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458507085760"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.8772283"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-015-0706-x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2010.0257"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00400-5"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.175"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2005.02.010"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-008-0473-0"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.21101\/cejph.a3407","article-title":"Selected aspects of tobacco control in Croatia","volume":"17","author":"Loubeau P. R.","year":"2009","journal-title":"Central European Journal of Public Health"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2006.00711.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1032"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph110606417"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt139"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.05.003"},{"key":"e_1_2_6_35_1","first-page":"369","article-title":"Saadat. Association between insertion\/deletion polymorphism in angiotension converting enzyme and susceptibility to schizophrenia","volume":"44","author":"Mazaheri H.","year":"2015","journal-title":"Iran Journal of Public Health"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2016.07.004"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2015.03.014"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0b013e3283518524"},{"key":"e_1_2_6_39_1","first-page":"36","article-title":"Pleiotropic effects of ACE polymorphism","volume":"19","author":"Nawaz S. K.","year":"2008","journal-title":"Biochemical Medicine"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.02.050"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2008.06.005"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2649"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903958106"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20703"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1788"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114844"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000156155.19270.F8"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21040"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01717829"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3.2.120"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.054635"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/13102818.2006.10817350"},{"key":"e_1_2_6_53_1","first-page":"312","article-title":"IFN\u2010\u03b2 alters neurotrophic factor expression in T cells isolated from multiple sclerosis patients \u2010 implication of novel neurotensin\/NTSR1 pathway in neuroprotection","volume":"6","author":"Soltys J.","year":"2014","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903602106"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282e9a51e"},{"key":"e_1_2_6_56_1","first-page":"77","article-title":"A large cross\u2010sectional study of health attitudes, knowledge, behaviour and risks in the post\u2010war Croatian population (the First Croatian Health Project)","volume":"25","author":"Turek S.","year":"2001","journal-title":"Collegium Antropologicum"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-015-9589-x"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2088-07.2007"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1797"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.02.026"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.3109\/03014460.2013.813584"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbrb3.600","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbrb3.600","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T14:33:50Z","timestamp":1749738830000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,14]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1002\/brb3.600"],"URL":"https:\/\/doi.org\/10.1002\/brb3.600","archive":["Portico"],"relation":{},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"type":"print","value":"2162-3279"},{"type":"electronic","value":"2162-3279"}],"subject":[],"published":{"date-parts":[[2016,11,14]]},"article-number":"e00600"}}