Sirtuin3 rs28365927 functional mutation confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population

Background Non-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 SNPs that may confer a risk for NAFLD in the Han Chinese population. Methods Based 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). Results In 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. Conclusion Sirtuin3 rs28365927 is an independent risk factor for NAFLD in the Han Chinese population.