Abstract
BackgroundNon-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. Although genetic traits are among the most important risks factors for NAFLD, the understanding of their influence is still quite limited. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population.MethodsBased on the “two-hit hypothesis”, candidate SNPs, including Sirtuin3 rs28365927, were genotyped by MassARRAY in B-type ultrasonography-proven NAFLD patients (n = 292) and healthy controls (n = 387).ResultsIn a model analysis of individuals matched based on gender and age that compared 223 NAFLD and 223 non-NAFLD patients, the rs28365927 GA + AA genotype was a significant risk factor for the development of NAFLD in a dominant model. Rs28365927 was significantly associated with a higher NAFLD risk in both an additive model (A vs G) and genotypic model (GA vs GG). Among the NAFLD patients, serum levels of total bilirubin (TBIL), DBIL direct bilirubin (DBIL) and glutamic-pyruvic transaminase (ALT) in rs28365927 A allele carriers (GA + AA) were 11.1, 14.7 and 41.5% higher, respectively, than in non-carriers (GG). Furthermore, among the NAFLD patients, the carriers of Rs28365927 allele A were positively correlated with higher ALT levels.ConclusionSirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population. The rs28365927 A allele significantly increased the ALT levels of NAFLD patients.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver-related death that affects a quarter of adults worldwide, with the highest prevalence in the Middle East (31.8%) and South America (30.5%) and the lowest in Africa (13.5%)
NAFLD includes a broad range of pathologic features, ranging from benign and reversible simple steatosis to more severe non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis and even hepatocellular carcinoma [3]
The allele and genotype distributions of the 17 single nucleotide polymorphisms (SNPs) in the NAFLD and non-NAFLD groups demonstrate that only the genotype distributions of Sirtuin3 rs28365927 showed significant differences between the two groups (P < 0.05) and the genotype distributions of Sirtuin3 rs28365927 were in accordance with the Hardy-Weinberg equilibrium (HWE) in both the NAFLD and non-NAFLD patients (Tables 1 and 3)
Summary
Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver-related death that affects a quarter of adults worldwide, with the highest prevalence in the Middle East (31.8%) and South America (30.5%) and the lowest in Africa (13.5%). The prevalence of NAFLD in China is 27.4% [1] This disease is characterized by an excess accumulation of fat (in the form of triglycerides) in the hepatocytes (> 5% fat content in the liver, referred to as steatosis), leading to non-alcoholic fatty liver [2]. NAFLD is a multifactorial disease with obvious individual susceptibility, and a number of risk factors have been identified, such as metabolic syndrome, sedentary lifestyle, diet, aging, gender, genetic factors and other conditions [2, 5,6,7,8,9,10,11]. Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population
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