Association of FTO gene variant (rs8050136) with type 2 diabetes and markers of obesity, glycaemic control and inflammation

Abstract

Summary 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.

Genetic variability in sodium-glucose cotransporter 2 influences glycemic control and risk for diabetic retinopathy in type 2 diabetes patients

“…It has been suggested that SGLT2 in retinal pericytes may have role of glucose sensor that controls cellular tone in response to changes in extracellular glucose concentrations (26). These findings may support the biological plausibility of our observations that genetic variability of SGLT2 may play a role in the development of diabetic retinopathy.…”

“…These findings may support the biological plausibility of our observations that genetic variability of SGLT2 may play a role in the development of diabetic retinopathy. It has been also show that glucose entry into pericytes increased twofold under hyperglycemia conditions (26). Such alterations in glucose supply could potentially change retinal energy metabolism and therefor result in complications (27).…”

“…Excessive SGLT2 mediated entry of glucose and sodium during high glucose conditions resulted in functional and morphological changes in retinal peri-cytes, but this effect was attenuated by nonselective SGLT inhibitor phlorizin (26). As the use of SGLT2 inhibitors is rapidly increasing in the treatment of T2D patients, their potential protective effect regarding the development of diabetic retinopathy through direct actions on retinal pericytes needs to be further investigated in clinical studies.…”

Precision medicine in the era of CRISPR-Cas9: evidence from Bosnia and Herzegovina

“…The tests are available to patients through physician referral and cover medical conditions, such as prenatal DNA characterization, thrombophilia and breast cancer risk, and genotyping of the spectrum of inherited disorders through cooperation with laboratories specialized in detecting rare hereditary diseases. Recently, several clinical studies reported the use of genetic tests for improved diagnosis of different diseases in BH population, such as rheumatoid arthritis (Klimenta et al, 2019), Type 2 diabetes (Semiz et al, 2014, Semiz et al, 2010, Bego et al, 2019, Dujic et al, 2016, Semiz et al, 2011, posttraumatic stress disorder (Kucukalic et al, 2019), psychiatric (Memic et al, 2018), and rare neurodegenerative disorders (Begic et al, 2019). These developments suggest an increased interest in clinical application of genetic testing in BH.…”

Biochemical and clinical characteristics of patients with primary aldosteronism – single centre experience

“…Aldosterone oversecretion is associated with an increased prevalence of metabolic disorders such as impaired glucose and lipid metabolism and insulin resistance, but also with an increased occurrence of cardiovascular, renal and central nervous system complications (6). Atrial fibrillation is found to be twelve times more frequent in PA than in essential hypertension (EHT), myocardial infarction 6.5 times and cerebrovascular infarction 4.2 times, independent of blood pressure and PA subtypes (7).…”