BACKGROUND: FTO, a gene recently discovered in genomewide associated studies for type 2 diabetes mellitus (T2D), play an important role in the management of energy homeostasis, nucleic acid demethylation and regulation of body fat mass by lipolysis. The aim of this study was to analyze the association of FTO rs8050136 A>C genetic variant with clinical and biochemical parameters of T2D in the population of West Balkan region (Bosnians and Herzegovinians and Kosovars). METHODS: The study included 638 patients with T2D and prediabetes and 360 healthy controls of both genders, aged from 40 to 65 years. Patients were recruited at the Clinical Centre University of Sarajevo, University Hospital of Clinical Centre in Banja Luka, General Hospital in Tešanj and Health Centre in Prizren. Genotyping of analyzed FTO polymorphism rs8050136 A>C was performed by qPCR allelic discrimination. RESULTS: Genotype frequencies of the analyzed polymorphism were comparable between patients with T2D, prediabetic patients, and healthy population. Logistic regression analyses didn't show significant association of FTO rs8050136 A allele with increased risk of T2D. However, risk A allele was significantly associated with higher levels of HbA1c, insulin, HOMA-IR index, diastolic blood pressure, and inflammatory markers (fibrinogen and leukocytes) as well as showed tendency of association with increased values of obesity markers (BMI, waist and hip circumference). CONCLUSIONS: Results of our study showed a significant association of FTO genetic variant rs8050136 A>C with the major markers of insulin resistance, obesity and inflammation, opening new avenues for solving many unclear questions in the pathogenesis of T2D.

UVOD: FTO, gen koji je u cjelogenomskim studijama povezanosti, nedavno otkriven kao kandidatni gen za tip 2 dijabetes (T2D), ima značajnu ulogu u upravljanju energetske homeostaze, demetilaciji nukleinskih kiselina i regulaciji indeksa tjelesne mase (ITM) tako što reguliše proces lipolize. Cilj studije je bio da analiziramo povezanost FTO rs8050136 A>C genetske varijante sa kliničkim i biohemijskim parametrima T2D u populacijama regiona Zapadnog Balkana (Bosancima i Hercegovcima i Kosovarima). METODE: U studiju je uključeno 638 pacijenata oboljelih od T2D, predijabetesa, i 360 zdravih kontrola, oba spola, starosti od 40 do 65 godina. Pacijenti se regrutovani u Kliničkom centru Univerziteta u Sarajevu, Univerzitetskoj bolnici Kliničkog centra u Banja Luci, Opštoj bolnici u Tešnju i Domu zdravlja u Prizrenu. Genotipizacija FTO genetskog polimorfizma rs8050136 A>C je analizirana korištenjem metode qPCR alelne diskriminacije. REZULTATI: Frekvencije genotipova analiziranog polimorfizma uspoređivane su između pacijenata sa T2D, predijabetesom i zdravih ispitanika. Također, rezultati logistike analize nisu pokazali značajnu povezanost A alela FTO rs8050136 polimorfizma sa povećanim rizikom razvoja T2D. Međutim, rizični A alel je pokazao značajnu asociranost sa višim vrijednostima HbA1c, inzulina, HOMA IR indeksa, diastolnog krvnog pritiska, i inflamatornih markera (fibrinogena i leukocita), kao i tendenciju povezanosti sa povišenim vrijednostima parametara gojaznosti (ITM, opseg struka i opseg kukova). ZAKLJUČAK: Rezultati naše studije pokazali su značajnu povezanost FTO genetske varijante rs8050136 A>C sa najbitnijim markerima inzulinske rezistencije, gojaznosti i inflamacije, otvarajući na taj način nove puteve i mogućnosti riješavanja mnogih nejasnih pitanja vezanih za patogenezu T2D.

Clinics for Endocrinology Diabetes and Metabolism Diseases University Clinical Centre of Sarajevo Sarajevo Bosnia and Herzegovina

Department of Biochemistry and Clinical Analysis Faculty of Pharmacy University of Sarajevo Sarajevo Bosnia and Herzegovina

Department of Pathophysiology Faculty of Pharmacy; University Sarajevo Sarajevo Bosnia and Herzegovina

Faculty of Engineering and Natural Sciences International University of Sarajevo Sarajevo Bosnia and Herzegovina

General Hospital of Tesanj Tesanj Bosnia and Herzegovina

Institute for Clinical Biochemistry and Diagnostics University Hospital Hradec Kralove Hradec Kralove Czech Republic

The Chair of Clinical Biochemistry Faculty of Pharmacy University of Ljubljana Ljubljana Slovenia

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