The existence of the robust associations between NAFLD and obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension, cardiovascular disease and sometimes even hepatocellular carcinoma have been presented based on a wide range of studies [1–3]. NAFLD is considered a significant problem that affects approximately 10–30% of the general population of variable ethnicities across all regions of the world [4, 5]. Intriguingly, the prevalence of NAFLD is 49–62% in patients with T2DM and 18–33% of patients with NAFLD have T2DM [6–8]. Whereas a large number of studies suggested that T2DM is an independent risk factor for NAFLD, T2DM has the potential to produce NAFLD condition in the presence of TG in liver tissue [9, 10].
Uncoupling protein 2 (UCP2) is a mitochondrial inner-membrane anion carrier protein involved in energy homeostasis, regulation of the insulin secretion, free fatty acid (FFA) concentrations as well as lipid metabolism [11, 12]. The UCP2 is widely expressed in human tissues, containing white adipose tissue, skeletal muscle, pancreatic islets and the central nervous system [13, 14]. Due to UCP2 notable capabilities to promote lipid gathering in the liver organ, stimulate protective neural mechanisms in acute ethanol intake [15, 16] and reinforce insulin resistance [17], its basic role in pathophysiology of liver disease and obesity has been accepted. Interestingly, researches have demonstrated that there is correlation between polymorphisms within the UCP2 gene and metabolic diseases, particularly T2DM and obesity [18]. Based studies, modifying of the expression of genes which regulate UCP-2 expression and functions is promising therapeutic approach for controlling insulin resistance, obesity and body-weight gain or body mass index (BMI) [19]. Importantly, genetic polymorphisms in UCP2, in particular 45 bp deletion/insertion (D/I), have been reported to be associated with obesity, BMI and T2DM in the general population [20].
Because of their high prevalence, increased morbidity and mortality, and social and economic burden, NAFLD and T2DM constitute an important public health problem [21–23]. Accordingly, recognizing of the molecular base of the NAFLD and T2DM is required to open new landscape toward novel and effective therapeutic approaches. To our knowledge, there are no data on the relationship between the 45-bp D/I polymorphism in the UCP2 gene and NAFLD and T2DM in population of North-West of Iran. The main purpose of the current study is response to this query whether there are associations between 45-bp ins/del polymorphism and susceptibility to NAFLD and T2DM in a North-West of Iran population or not.