Abstract
Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.
Highlights
The studies on non-alcoholic fatty liver disease (NAFLD) have rapidly increased since the term non-alcoholic steatohepatitis was first introduced by Ludwig et al [1]
The differences in the parameters of body mass index (BMI), haemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL) cholesterol, total cholesterol, triglycerides, AST, alanine transferase (ALT) and gamma-glutamyl transpeptidase (GGT) between the two groups reflect the nature of the selection of the cases and controls
The BMI, HbA1c, waist circumference, triglycerides, systolic, and diastolic blood pressure were significantly higher in the non-alcoholic steatohepatitis (NASH) group (p,0.05) as compared to the simple steatosis group
Summary
The studies on non-alcoholic fatty liver disease (NAFLD) have rapidly increased since the term non-alcoholic steatohepatitis was first introduced by Ludwig et al [1]. NAFLD, defined as fatty accumulation of the liver without significant alcohol intake, ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis [2]. The histological features of NAFLD include steatosis, lobular inflammation, hepatocellular ballooning and fibrosis [3]. There is only one study of AGTR1 polymorphism and its association with the occurrence of NAFLD. Five variants of AGTR1(rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were revealed to be strongly associated with risk of NAFLD [15]. The deletion of angiotensin II type 1 receptor in animals was associated withdecreased hepatic steatosis. AGTR1 may be an important regulator of steatosis in the liver [16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
