Abstract
ObjectivePatients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease.MethodsWe enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured.ResultsOnly adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 μg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively).ConclusionsIn patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with hypoadiponectinemia. Low serum adiponectin level may precipitate liver steatosis in patients with type 2 diabetes.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in many countries
Adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001)
Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively)
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in many countries. NAFLD is the hepatic manifestation of metabolic syndrome and is associated with obesity, type 2 diabetes mellitus, dyslipidemia, high blood pressure, insulin resistance and cardiovascular disease [1,2,3]. Patients with type 2 diabetes and NAFLD have a higher prevalence of coronary, cerebrovascular and peripheral vascular diseases than patients with diabetes but without NAFLD [9,10]. The 2011 National Diabetes Fact Sheet revealed that more than 65% of all deaths in patients with type 2 diabetes are caused by cardiovascular disease. Adams et al have shown that cardiovascular disease accounts for about 25% of deaths in patients with NAFLD versus 13% of deaths in patients with other liver diseases [11]. NAFLD may result in an increased risk of mortality, especially due to cardiovascular disease, in patients with type 2 diabetes
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