ASSOCIATION OF SEROTONIN TRANSPORTER GENE POLYMORPHISM AND METABOLIC SYNDROME IN DEPRESSION

Uvod: Depresija je čest psihijatrijski poremećaj kojeg karakteriziraju ponovljene epizode depresivnog raspoloženja, ali i različiti somatski simptomi, kao što su metabolički simptomi koji mogu rezultirati razvojem metaboličkog sindroma. Etiologija depresije još nije potpuno poznata. Smatra se da su geni uključeni u kodiranje proteina važnih za regulaciju i funkciju serotonergičkog (5-HT) sustava, kao što je gen za serotoninski transporter (5HTT) i njegov funkcionalni polimorfizam 5-HTTLPR (polimorfna regija vezana za gen serotoninskog transportera), povezani s depresijom. Cilj istraživanja: Cilj istraživanja bio je utvrditi postoji li povezanost 5-HTTLPR i metaboličkog sindroma i/ili pojedinih sastavnica metaboličkog sindroma u depresivnih bolesnika. Naime, očekivana je veća zastupljenost SS genotipa, odnosno S alela obzirom na 5-HTTLPR kod bolesnika s metaboličkim sindromom prema onima koji nisu razvili metabolički sindrom. Ispitanici i metode: Istraživanje je uključilo 202 depresivna bolesnika sa i 204 depresivna bolesnika bez metaboličkog sindroma. Dijagnoza depresije postavljena je prema kriterijima MKB-10, a metaboličkog sindroma prema kriterijima SZO. Komponente metaboličkog sindroma određene su rutinskim laboratorijskim metodama. Genotipizacija je provedena lančanom reakcijom polimeraze. Rezultati su obrađeni pomoću Kruskal-Wallisove analize rangova i Dunnovog testa, ili Mann Whitneyevog testa, Spearmanovog koeficijenta korelacije i višestruke linearne regresije. Rezultati: Nisu utvrđene značajne razlike u učestalosti 5-HTTLPR genotipova ili alela između depresivnih bolesnika sa i bez metaboličkog sindroma. Međutim, nosioci LL genotipa imali su značajno viši dijastolički tlak i opseg struka od nosioca drugih genotipova. Druge komponente metaboličkog sindroma (sistolički tlak, koncentracije triglicerida, glukoze i HDL kolesterola, izlučivanje albumina) nisu bile povezane s polimorfizmom 5-HTTLPR u depresivnih bolesnika. Zaključak: 5-HTTLPR polimorfizam nije značajno povezan s metaboličkim sindromom u depresivnih bolesnika. Utvrđena je značajna povezanost 5-HTTLPR i sastavnica metaboličkog sindroma (dijastoličkog tlaka i opsega struka) upućujući da je LL genotip obzirom na 5-HTTLPR rizičan za viši dijastolički tlak i veći opseg struka. Ti podatci upućuju da 5-HTTLPR polimorfizam ima određenu ulogu u razvoju pojedinih komponenti metaboličkog sindroma u depresivnih bolesnikaIntroduction: Depression is frequent psychiatric disorder characterized by the reccurent episodes of depressed mood, but also with different somatic symptoms such as metabolic symtpoms that might result in development of metabolic syndrome. Etiology of depression is not completely known. It is assumed that genes coding for proteins important for regulation and fuction of serotonin (5-HT) system, such as a gene for serotonin transporter (5HTT), and its functional polymorphism 5-HTTLPR (serotonin-transporter-linked polymorphic region), are associated with depression. Aim of study: Study aimed to determine association between 5-HTTLPR and metabolic syndrome and/or components of metabolic syndrome in depressed patients. Namely, we expected that patients with metabolic syndrome will be more frequently carriers of the 5- HTTLPR SS genotype or S allele compared to depressed patients without metabolic syndrome. Subjects and methods: The study included 202 depressed patients with and 204 depresssed patients without metabolic syndrome. Diagnosis of depression was made according to the ICD-10 criteria, and metabolic syndrome according to the criteria of the WHO, and use of routine laboratory and clinical measurements. Genotyping was determined using PCR. Results were analyzed with Kruskal-Wallis ANOVA and Dunn test, Mann Whitney test, Spearman's coefficient of correlation and multiple linear reggression. Results: 5-HTTLPR polymorphism was not significatly associated with metabolic syndrome in depressed patients. However, carriers of the LL genotype had significantly higher diastolic blood pressure and weist circumference than other genotype carriers. Other components of the metabolic syndrome (sistolic blood pressure, triglycerides, glucose, HDL cholesterol concentrations and albumines) were not significantly associated with 5-HTTLPR polymorphism in deppressed patients. Conclusion: 5-HTTLPR polymorphism is not significantly associated with metabolic syndrome in depressed patients. Significant association between 5-HTTLPR and components of metabolic syndrome (diastolic blood pressure and weist circumference) was found, suggesting that LL genotpye of the 5-HTTLPR is a risk genotipe for higher diastolic blood pressure and increased weist circumference. These data suggest that 5-HTTLPR polymorphism has particular role in development of specific components of metabolic syndrome in depressed patients