Association between four common microRNA polymorphisms and the risk of hepatocellular carcinoma and HBV infection

Abstract

microRNAs (miR/miRNAs) have been demonstrated to function as tumor suppressors and oncogenes, and miRNA polymorphisms may have a role in cancer development. The present study aimed to investigate the association between the miR-146aG>C, miR-149C>T, miR-196a2C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) infection. A total of 271 patients with HCC and 532 healthy control participants were enrolled in the present study. miR-146aG>C, miR-149C>T, miR-196a2C>T and miR-499A>G polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. A significant difference was identified in the genotype frequency of miR-196a2C>T in the patients in the case group compared with the control group (χ2=6.88; P=0.032). Compared with the CC genotype, the miR-196a2 TT genotype was associated with a significantly reduced risk of HCC [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.38–0.99], and a significantly reduced risk was also found in the dominant (OR, 0.69; 95% CI, 0.49–0.98) and recessive (OR, 0.70; 95% CI, 0.46–1.02) models. Moreover, individuals with HBV who were carrying the miR-196a2 CT and TT genotypes had a significantly reduced risk of HCC (OR, 0.62; 95% CI, 0.41–0.95; and OR, 0.39; 95% CI, 0.20–0.73, respectively). In conclusion, the present study found that the miR-196a2C>T polymorphism has a protective effect in patients with HCC, particularly in those with HBV infection.

The Association of Common Functional Polymorphisms in Mir-146a and Mir-196a2 and Hepatocellular Carcinoma Risk

“…One study in the present meta-analysis did not provide definite criteria for the HCC diagnosis. 36 The genotype distributions of the controls in 3 studies were inconsistent with HWE for miR-146a rs2910164 polymorphism 23 , 24 , 27 and 2 were inconsistent with HWE for miR-196a2 rs11614913 polymorphism. 24 , 27 …”

“…For analyses of pooling more than three studies, the significance of ORs was not influenced materially by omitting any single study (data not shown). For the miR-146a rs2910164 polymorphism, sensitivity analysis was further performed by omitting the studies by Shan et al, Kou et al, and Zhou et al 23 , 24 , 27 in which the control populations were not in accordance with HWE. The significance of all ORs was not altered after excluding these 3 studies.…”

“…The significance of all ORs was not altered after excluding these 3 studies. For the miR-196a2 rs11614913 polymorphism, sensitivity analysis was also performed by excluding those 2 studies by Kou et al and Zhou et al 24 , 27 in which the control populations were deviated from HWE, and the significance of all ORs was also not altered.…”

“…In the present study, the genotype distributions of the controls in 3 studies were inconsistent with HWE for miR-146a rs2910164 polymorphism. 23 , 24 , 27 Hence, we carried out subgroup analysis by HWE in controls. When excluding the studies that were inconsistent with HWE, the results were persistent and robust, suggesting that this factor probably had little effect on the overall estimates.…”

Hepatitis B Virus Infection, MicroRNAs and Liver Disease

“…In another independent study they found the T allele in the miR-219-1 promoter to be strongly associated with HBV clearance [ 70 ]. On the other hand, Kou et al [ 71 ] found that the miR-196a2C>T polymorphism imparts protection in HBV-related HCC. Yu et al .…”