Non-alcoholic fatty liver disease (
NAFLD) is a hepatic manifestation of
metabolic syndrome and major cause of chronic
liver disease in developed countries. Its prevalence is increasing in parallel with the prevalence of
obesity and other components of the
metabolic syndrome. As the liver is central to the clearance and catabolism of circulating advanced glycosylation end-products (AGEs), AGEs and their cognate receptors-RAGE (receptor for AGEs) system might be involved in
NAFLD in obese patients. To examine this, we investigated four common polymorphisms of RAGE gene: 1704G/T (rs184003), G82S (rs2070600), -374T/A (rs1800624) and -429T/C (rs1800625) in 340 obese patients with
metabolic syndrome. and
protein levels of AGE and RAGE. This is the first study to describe association of 4 common polymorphisms with non-
alcoholic steatohepatitis (NASH) as well as to examine
protein levels of RAGE and AGE. Univariate analysis showed patients carrying the rs1800624 heterozygote genotype (AT) exhibited 2.36-fold increased risk of NASH (odds ratio (OR) = 2.36; 95% confidence interval (95% CI): 1.35-4.19) after adjusting for confounders. The minor allele -374 A has been shown to suppress the expression of RAGE
protein. The
protein levels of esRAGE, total sRAGE and AGE
protein levels did not correlate with each other in obese patients with no
liver disease, indicative of RAGE signaling playing an independent role in liver injury. In obese patients with non-NASH
NAFLD and NASH respectively, esRAGE
protein showed strong positive correlation with total sRAGE
protein. Further, haplotype analysis of the 4 SNPs, indicated that haplotype G-A-T-G was significantly associated with 2-fold increased risk for NASH (OR = 2.08; 95% CI: 1.21-3.5; P = 0.006) after adjusting for confounders. In conclusion, the presented data indicate that the G-A-T-G haplotype containing minor allele at position -374 A and major allele at position -429T, 1704G, and G82S G could be regarded as a marker for NASH.