High-resolution melting analysis reveals genetic polymorphisms in MicroRNAs confer hepatocellular carcinoma risk in Chinese patients
- Equal contributors
1 Center for Gene Diagnosis, Medical Research Center, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei 430071, China
2 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA
3 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
BMC Cancer 2014, 14:643 doi:10.1186/1471-2407-14-643Published: 31 August 2014
Although several single-nucleotide polymorphisms in microRNA (miRNA) genes have been associated with primary hepatocellular carcinoma, published findings regarding this relationship are inconsistent and inconclusive.
The high-resolution melting (HRM) analysis was used to determine whether the occurrence of the SNPs of miR-146a C > G (rs2910164), miR-196a2 C > T (rs11614913), miR-301b A > G (rs384262), and miR-499 C > T (rs3746444) differs in frequency-matched 314 HCC patients and 407 controls by age and sex.
The groups’ genotype distributions of miR-196a2 C > T and miR-499 C > T differed significantly (P < 0.01), both of them increased the risk of HCC in different dominant genetic models (P < 0.01); compared with individuals carrying one or neither of the unfavorable genotypes, individuals carrying both unfavorable genotypes (CT + CC) had a 3.11-fold higher HCC risk (95% confidence interval (CI), 1.89–5.09; P = 7.18 × 10−6). Moreover, the allele frequency of miR-499 C > T was significantly different between the two groups, and the HCC risk of carriers of the C allele was higher than that of carriers of the T allele (odds ratio, 1.53; 95% CI, 1.15-2.03; P = 0.003). Further, we found that the activated partial thromboplastin time (APTT) in HCC patients with miR-196a2 CC genotype was longer than patients with TT genotypes (P < 0.05), and HCC patients with miR-499 C allele had higher serum levels of direct bilirubin, globulin, γ-glutamyltranspeptidase, alkaline phosphatase, and lower serum cholinesterase (P < 0.05).
Our findings suggest that the SNPs in miR-196a2 C > T and miR-499 C > T confer HCC risk and that affect the clinical laboratory characteristics of HCC patients.