Key result
AGTR1 gene variants show no overall association with NAFLD despite potential protection in Indian subgroups.
Why the study?
The role of AGTR1 gene polymorphisms in susceptibility to NAFLD and their interaction with PNPLA3 gene variants in a multi-ethnic population was unclear.
Are AGTR1 gene polymorphisms associated with susceptibility to NAFLD and fibrosis severity?
Case-Control (n=342)
No
Are AGTR1 gene polymorphisms associated with susceptibility to NAFLD and fibrosis severity?
Odds Ratio: 0.82 (95% CI 0.48–1.37)
p-value: p=0.445
Specific AGTR1 gene polymorphisms may influence susceptibility to NAFLD and fibrosis severity, particularly in certain ethnic groups like Indians.
AGTR1 variants lack NAFLD association overall; leaves open ethnic-specific effects in Indians for validation.
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.
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Zain et al. (2013) conducted a case-control in Non-alcoholic fatty liver disease (NAFLD) (n=342). AGTR1 gene polymorphisms vs. Healthy controls was evaluated on Susceptibility to NAFLD (rs2276736 variant) (OR 0.82, 95% CI 0.48-1.37, p=0.445). Five variants of the AGTR1 gene showed no significant association with susceptibility to NAFLD in the overall multi-ethnic population (OR 0.82, p=0.445 for rs2276736), although some variants appeared protective in the Indian subgroup.
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