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LABORATORIO CLÍNICO The association between miRNA SNPs and HCC - W. Li et al Table 1. The miRNA SNPs investigated in this study patients, Pearson chi-square test of independence was performed. For quantitative clinical indexes, ANOVA tests were carried out when the data had homogeneity of variance, while nonparametric test was applied to analyze the data with heterogeneity of variance or non-normal distribution. A p-value < 0.05 was considered as significant, and all statistical 510 tests were two-sided. Results Sample overview There were 1,018 subjects enrolled in our study, including 498 HCC patients and 520 controls. In the cases group, HBsAg positive patients accounted for 82.7%. General characteristics of all subjects are listed in Table 2. It was shown that age, gender and smoking status were significantly different between cases and controls, while drinking status showed no difference between both groups. In this study, we investigated 2 microRNA SNPs, that is rs13299349 and rs10061133. The two SNPs were successfully genotyped in 1,015 and 1,010 subjects respectively. Association between the miRNA SNPs and susceptibility to hepatocellular carcinoma After adjusting for confounding factors such as sex, age and smoking by binary logistic regression, we found that there was a significant association between rs13299349 in miRNA3152 and the risk of HCC (Table 3). The genotype of AA or A allele associated significantly to an increased risk of HCC (AA: OR (95% CI) = 5.286 (1.059-26.379), P = 0.042; A allele: OR (95% CI) = 1.386 (1.031- 1.864), P = 0.031) compared with the genotype of AG+GG or G allele. This trend was also showed in the HBV-related HCC patients (AA: OR (95% CI) = 9.657(1.105-84.395); A allele: OR (95% CI) = 1.396 (1.008-1.934), P = 0.045). Thus, this indicated that the recessive model might suit its role in the formation of the HCC and the HBV-related HCC. Moreover, we found that there was statistically significant association between rs10061133 in miRNA449b and the susceptibility to HCC (Table 3). The G allele was significantly associated with increased risk of HCC (G allele: OR (95% CI) = 1.234 (1.002-1.520), P = 0.048) compared with A allele. There was no significance in AG and GG genotype patients. Association between the miRNA SNPs and clinical indexes in HCC patients As shown in Table 4, the relation between the SNPs and the clinical indexed consisted of the number, size, AFP, total bilirubin, direct bilirubin, indirect bilirubin, ALT, AST, HBV-DNA, CEA and CA199 was also explored. However, it was only detected that rs13299349 was significantly related to the size and the number of tumor foci. The proportion of tumor size ≥ 5 cm in A allele was 71.2%, whereas in G allele it was 56.3% (P = 0.036). In the meantime, the proportion of the multiple number of tumor foci in AA, GG and AG genotype was 50%, 13.99% and 3.51% respectively (P = 0.003). Both results were consistent with the correlation of AA genotype/A allele to the increased risk of HCC. The other SNPs had no association to the clinical indexes. SNP ID Substitutes SNP location Chromosome start-stop site miRNA Location Amplification primer 2 Amplification primer 1 Extension primer rs13299349 A/G 18573360 chr9: 18573304- 18573377 hsa-mir- 3152 mat ACGTTGGATG AGACTAGGCT TCCCTGTGTT ACGTTGGATG ACTTCCTCCT TAGATGGGTG tcctTGCAGAG TTATTGCCC rs10061133 A/G 54466544 chr5: 54466474- 54466570 hsa-mir- 449b mat ACGTTGGATG TAGTTGTGGC TGCTGACTTG ACGTTGGATG AATCGGCAGT GACCTGAATC GAATCAGGTAGG CAGTGTAT Rev Med Chile 2016; 144: 508-515


Abril 2016
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