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Association between two genetic variants in miRNA and primary liver cancer risk in the Chinese population
Juan Zhou1, Ruixue Lv, Xingbo Song
1Division of Molecular Medicine, Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Abstract:
MicroRNAs (miRNAs) play an important role in the growth and development of human beings. Single nucleotide polymorphisms (SNPs) within miRNA could change their production or affinity with target genes, thus leading to malignant diseases. This case-control study conducted in Western China aimed to explore the relationship between polymorphisms in miR-146a (rs2910164 G>C) and miR-499 (rs3746444 T>C) and primary liver cancers in the Chinese population. 186 primary liver cancer cases and 483 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism. No significant differences were observed between distributions of the two SNPs and susceptibility of primary liver cancer or diverse clinicopathologic features. However, we found that patients with genotype CG of the SNP in miR-146a tended to have earlier onset and better liver function than patients with genotype CC (average age: 49.9 vs. 54.9, p=0.038; average Child-Pugh grade: 5.55 vs. 6.15, p=0.021), and further analysis showed that patients who had at least one G allele were diagnosed at an earlier age (average age: 49.6 vs. 54.9, p=0.022) and had better liver function (average Child-Pugh grade:5.60 vs. 6.15, p=0.026). Our data suggested lack of association between the two SNPs and primary liver cancer risk, though, interestingly, the miR-146a SNP may influence the age of onset and Child-Pugh grade.
Insights
Single nucleotide polymorphisms (SNPs) in miR-146a and miR-499 were not linked to primary liver cancer risk in Chinese adults. However, miR-146a SNPs may influence earlier disease onset and liver function.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) are crucial regulators of human growth and development.
- Single nucleotide polymorphisms (SNPs) in miRNAs can alter gene expression and target affinity, potentially contributing to diseases like cancer.
- Primary liver cancer remains a significant global health concern, necessitating research into its genetic underpinnings.
Purpose of the Study:
- To investigate the association between specific polymorphisms in miR-146a (rs2910164 G>C) and miR-499 (rs3746444 T>C) and the risk of primary liver cancer in a Western Chinese population.
- To explore potential correlations between these miRNA SNPs and various clinicopathological features of liver cancer.
Main Methods:
- A case-control study was conducted with 186 primary liver cancer patients and 483 healthy controls from Western China.
- Genotyping of the selected SNPs in miR-146a and miR-499 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
- Statistical analyses were employed to compare SNP distributions between cases and controls and to assess associations with clinicopathological characteristics.
Main Results:
- No significant association was found between the studied polymorphisms in miR-146a and miR-499 and the susceptibility to primary liver cancer.
- The distribution of these SNPs did not correlate with diverse clinicopathological features of the disease.
- Interestingly, patients with the miR-146a CG genotype exhibited an earlier age of onset (49.9 years) and better liver function (Child-Pugh grade 5.55) compared to the CC genotype (54.9 years and 6.15, respectively).
- Further analysis revealed that individuals carrying at least one G allele in miR-146a were diagnosed at a younger age (49.6 years) and had improved liver function (Child-Pugh grade 5.60) compared to those without the G allele (54.9 years and 6.15, respectively).
Conclusions:
- The investigated SNPs in miR-146a and miR-499 are not significantly associated with the risk of developing primary liver cancer in the studied Chinese population.
- The miR-146a rs2910164 polymorphism may play a role in influencing the age of onset and the severity of liver dysfunction (Child-Pugh grade) in liver cancer patients.
- Further research is warranted to elucidate the functional mechanisms underlying the observed influence of miR-146a SNPs on disease progression and liver function.
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