Association of Adiponectin Gene Polymorphism with Nonalcoholic Fatty Liver Disease in Taiwanese Patients with Type 2 Diabetes

• Published in: PloS one Vol. 10; no. 6; p. e0127521
• Main Authors: Hsieh, Ching-Jung, Wang, Pei Wen, Hu, Tsung Hui
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.06.2015; Public Library of Science (PLoS)
• Subjects: Adiponectin; Adiponectin - blood; Adiponectin - genetics; Alanine; Alanine transaminase; Alcohol use; Alleles; Anthropometry; Aspartate; Aspartate aminotransferase; Body fat; Body mass; Body mass index; Body size; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Demography; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Endocrinology; Fasting; Fatty liver; Female; Gene Frequency - genetics; Gene polymorphism; Genes; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genotypes; Glucose; Heart diseases; Hemoglobin; Hemoglobins; Hepatitis; Hepatology; High density lipoprotein; Hospitals; Humans; Insulin resistance; Internal medicine; Leptin; Lipids; Lipoproteins (high density); Lipoproteins (low density); Liver; Liver diseases; Low density lipoprotein; Low density lipoproteins; Male; Medicine; Metabolic syndrome; Middle Aged; Molecular chains; Molecular weight; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - genetics; Obesity; Pathogenesis; Patients; Phospholipase; Polymorphism; Polymorphism, Single Nucleotide - genetics; Prevalence studies (Epidemiology); Single nucleotide polymorphisms; Single-nucleotide polymorphism; Steatosis; Subgroups; Taiwan; Type 2 diabetes; Taiwan; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0127521

Patients 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. We 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. Only 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). In 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.