Interaction Between AGTR1 and PPARγ Gene Polymorphisms on the Risk of Nonalcoholic Fatty Liver Disease.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is an important public health issue worldwide. Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPARγ and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults. METHODS: Seven single nucleotide polymorphisms (SNPs) of the PPARγ gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD. RESULTS: After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPARγ variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPARγ and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p < 0.05) except the 2-, 10-, 11-, and 12-locus models. Further, among the 10 SNPs negatively associated with NAFLD, the four-locus model (rs13431696 and rs3856806 in PPARγ, and rs5182, rs1492100 in ATGR1) and the five-locus model (rs9817428, rs1175543, rs13433696, and rs2920502 in PPARγ, and rs1492100 in ATGR1) were closely related with NAFLD susceptibility (p = 0.019 and p = 0.048, respectively). CONCLUSION: Our present study suggests that interactions among multiple AGTR1 and PPARγ polymorphisms are associated with the risk of NAFLD in the Chinese population.

Identification and characterization of interferon signaling-related microRNAs in occult hepatitis B virus infection.

BACKGROUND: Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis. METHODS: Twenty serum samples for training test (10 healthy controls and 10 OBI patients) and 438 validation serum samples from healthy controls, asymptomatic HBsAg carriers (ASC), and chronic hepatitis B (CHB) and OBI patients were collected. Expression levels of 32 IFN signaling-related miRNAs were analyzed in training and validation sets of samples using RT-qPCR. RESULTS: Among 32 IFN signaling-related miRNAs, decreased miR-122 levels and increased miR-130a levels were detected in training OBI samples. Furthermore, the results from validation test showed that the mean serum miR-122 and miR-130a level was 2.28 ± 0.96 and 3.11 ± 0.93 in OBI subjects, respectively. Compared to the healthy controls, ASC and CHB patients, miR-122 levels were significantly downregulated, while miR-130a levels were significantly upregulated in OBI patients. ROC analysis indicated that miR-122 + miR-130a could differentiate OBI from healthy controls, ASC, and CHB (≥ 0.87 of AUC). CONCLUSIONS: Our study suggested that decreased serum miR-122 level and increased miR-130a level were significantly associated with OBI. Moreover, a combination of miR-122 and miR-130a could be served as a potential marker for OBI diagnosis.