Erberk Nurper ÖZEN, ORHAN MURAT KOÇAK, MEHMET TOLGA DOĞRU, D. Beyza SAYIN

Anjiotensin dönüştürücü enzim polimorfizminin anksiyete ve depresyon düzeyine etkisi

Amaç: Çalışmamızda anjiotensin dönüştürücü enzim (ADE) gen polimorfizminin delesyon (D) ve insersiyon (I) alelleri ile anksiyete ve depresyon düzeyleri arasındaki ilişkiye bakılması amaçlanmıştır. Yöntem: Bu çalışma kesitsel bir çalışma olup, çalışma grubunu oluşturan olgular göğüs ağrısı yakınması ile bir üniversite hastanesi kardiyoloji polikliniğine başvuran hastalar arasından seçilmiştir. ADE’nin periferik düzeneklerle hipertansiyon (HT) ve koroner arter hastalığı (KAH) üzerine etkisi iyi bilindiğinden, seçilen hastaların bu tanı gruplarından bağımsız olması amaçlanmıştır. Böylece, ADE’nin olası santral düzenekler üzerinden anksiyete ve depresyon düzeylerini etkiliyor olabileceğinin tartışılması hedeflenmiştir. Çalışma grubunda, yaş ortalaması 51.92±9.78 olan 26 kadın ve yaş ortalaması 49.77±10.01 olan 13 erkek olmak üzere toplam 39 hasta yer almıştır. Olgular önce kardiyolojik açıdan değerlendirilmiş ve ayrıntılı incelemeleri yapılmıştır. Ardından psikiyatri polikliniğinde Beck Depresyon Ölçeği (BDÖ) ve Beck Anksiyete Ölçeği (BAÖ) uygulanmıştır. Hastalardan alınan kan örnekleri genetik polimorfizmlerinin değerlendirilmesi için genetik laboratuarına gönderilmiştir. Elde edilen sonuçlar MANOVA, Post Hoc Bonferroni Testi, Kruskal-Wallis Testi ve Fischer’s Exact Testi ile değerlendirilmiştir. Bulgular: BDÖ puanları açısından, ADE yüksek aktivitesi ile ilişkili olan D/D polimorfizmi ile düşük aktivite ile ilişkili olan I/I polimorfizmi ve orta düzeyde aktivite gösteren I/D polimorfizmi arasında anlamlı ilişki bulunmuştur (sırasıyla p=0.010 ve p=0.030). BAÖ puanları açısından ise sadece D/D polimorfizmi ile I/I polimorfizmi arasındaki fark anlamlı bulunmuştur (p=0.002). Sonuç: ADE genotiplerinden enzim aktivitesinin yüksekliği ile ilgili D aleline sahip olan bireylerde HT sıklığının arttığı bilinmektedir. Çalışmamızda, HT ve KAH olmayan bireylerde D aleline sahip olmanın, anksiyete ve depresyon düzeyinde artışla ilişkisi gösterilmiştir. ADE’nin depresyon ve anksiyete üzerine santral etkisi, HT üzerine olan periferik etkisinden farklı ve bağımsız olabilir.

The effect of the angiotensin-converting enzyme gene polymorphism on the depression and anxiety levels

Objective: We aimed to investigate the relationship between the angiotensin-converting enzyme (ACE) gene insertion (I) and deletion (D) polymorphism and the levels of anxiety and depression. Methods: This is a cross- sectional study, which included the cases who admitted a university hospital cardiology department with the complaint of chest pain without cardiac etiology. It is well known that there is a strong connection between the ACE and hypertension (HT) and coronary arterial diseases (CAH) among peripheral mechanisms. Hence, the subjects included the study were preferred that have no cardiovascular diseases at that time. In this way, it was aimed to conclude that ACE might have an effect on the levels of the anxiety and depression via possible central mechanisms. The study group, which was total 39 patients, was constituted that 26 female with the mean age 51.92±9.78 and 13 male with the mean age 49.77±10.01. Their first examination was carried out in cardiology department and performed the necessary techniques. Then the subjects were given the Beck Depression Inventory and Beck Anxiety Inventory in psychiatry department. Serum samples of the group were transferred to genetic laboratory. The statistical analyses were performed by SPSS 15.0 for Windows. MANOVA, Post Hoc Bonferroni Test, Kruskal Wallis Test and Fischer’s Exact Test were used with a related manner. Results: It was found that D/D polymorphism that is related with the high ACE activity has a significant association between I/I polymorphism that is related with the low ACE activity and D/I polymorphism that is related with the moderate ACE activity in terms of BDI scores (p=0.010 and p=0.030, respectively). On the other hand, in the BAI scores, D/D polymorphism was seen to be a significant association only with I/I polymorphism (p=0.002). Conclusion: It is well established that the ACE gene D polymorphism could be associated with the essential hypertension in the human. In our study, significant relation with the D genotyping and the levels of depression and anxiety were observed in a group, which have no cardiovascular problem detected. It could be suggested that the effect of the ACE system on the arterial pressure may have a role in a different manner from the central mechanisms which may be related the anxiety and depression etiology.

PDF

___

1. Bader M, Ganten D. Update on tissue reninangiotensin system. J Mol Med 2008; 86:615-621.
2. Jeunemaitre X. Genetics of renin-angiotensin system. J Mol Med 2008; 86:637-641.
3. Bandelow B, Saleh K, Pauls J, Domschke K, Wedekind D, Falkai P. Insertion/deletion polymorphism in the gene for angiotensin converting enzyme (ACE) for panic disorder: a gender-specific effect. World J Biol Psychiatry 2007; 10:1-5.
4. Hong CJ, Wang YC, Tsai SJ. Association study of angiotensin I-converting enzyme polymorphism and symptomatology and antidepressant response in major depressive disorders. J Neural Transm 2002; 109:1209-1214.
5. Xia H, Lazartigues E. Angiotensin-converting enzyme in the brain: properties and future directions. J Neurochem 2008; 107:1482-1494.
6. Saab YB, Gard PR, Yeoman MS, Mfarrej B, ElMoalem H, Ingram MJ. Renin-angiotensin-system gene polymorphisms and depression. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31:1113-1118.
7. Furlong RA, Kerametipour M, Ho LW, Rubinsztein JS, Michael A, Walsh C, et al. No association of an insertion/deletion polymorphism in the angiotensin converting enzyme gene with bipolar or unipolar affective disorders. Am J Med Genet (Neuropsychiatr Genet) 2000; 96:733-735.
8. Shimizu E, Hashimoto K, Kobayashi K, Mitsumori M, Ohgake S, Koizumi H, et al. Lack of association between angiotensin-I converting enzyme insertion/deletion functional polymorphism and panic disorder in humans. Neurosci Lett 2004; 363:81-83.
9. Baghai TC, Schule C, Zwanzger P, Zill P, Ella R, Eser D, et al. Influence of a functional polymorphism within the angiotensin-I converting enzyme gene on partial sleep deprivation in patients with major depression. Neurosci Lett 2003; 339:223-226.
10. Baghai TC, Schule C, Zill P, Deiml T, Eser D, Zwanzger P, et al. The angiotensin-I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men. Neurosci Lett 2004; 363:38-42.
11. Saavedra JM, Benicky J. Brain and peripheral angiotensin II play a major role in stress. Stress 2007; 10:185-193.
12. Nahshoni E, Aravot D, Aizenberg D, Sigler M, Zalsman G, Strasberg B, et al. Heart rate variability in patients with major depression. Psychosomatics 2004; 45:129-134.
13. Chrousos GP, Kino T. Glucocorticoid action networks and complex psychiatric and/or somatic disorders. Stress 2007; 10:213-219.
14. Cimilli C. Kardiyovasküler sistemin psikosomatik bozuklukları. Türkiye Klinikleri Psikiyatri 2008; 1:47-56.
15. Rutledge T, Hogan BE. A quantitative review of prospective evidence linking psychological factors with hypertension development. Psychosom Med 2002; 64:758-766.
16. Güleç MY, Hocaoğlu Ç, Durmuş İ. Kalple ilişkili olmayan göğüs ağrısı olan hastalarda psikiyatrik eştanı. Klinik Psikiyatri 2007; 10:7-13.
17. Beck AT. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4:561-571.
18. Hisli N. Beck Depresyon Envanterinin üniversite öğrencileri için geçerliği, güvenirliği. Psikoloji Dergisi 1989; 7:3-13.
19. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol 1988; 56:893-897.
20. Ulusoy M, Şahin NH, Erkmen H. Turkish version of the Beck Anxiety Inventory: Psychometric properties. J Cogn Psychother 1998;12:163-172.
21. Rigat B, Hubert C, Corvol P, Soubrier R. PCR detection of insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipepdidyle carboxypeptidase 1). Nucl Acids Res 1992; 20:1433.
22. Nacak M, Davutoglu V, Soydinc S, Dinckal H, Turkmen S, Erbagci B, et al. Association between angiotensin converting enzyme gene polymorphism and coronary artery disease in individuals of the South-Eastern Anatolian population. Anadolu Kardiyol Derg 2004; 4:45-51.
23. Bondy B, Baghai TC, Zill P, Schule C, Eser D, Deiml T, et al. Genetic variants in the angiotensinI converting enzyme (ACE) and angiotensin II receptor (AT1) gene and clinical outcome in depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:1094-1099.
24. Çataloluk O, Nacak M, Savaş HA, Tutkun H, Zoroğlu SS, Herken H, et al. Angiotensin converting enzyme gene polymorphism and its association to bipolar affective disorder in Turkish patients. Neurology, Psychiatry and Brain Research 2003; 10:129-132.
25. Konuk N, Atik L, Simsekyilmaz O, Dursun A, Acikgoz S. Association of angiotensin converting enzyme gene polymorphism and affective disorders in Turkish patients. Aust N Z J Psychiatry 2006; 40:717-718.