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ABSTRACT
Background
The elongation factor Tu GTP-binding domain-containing 2 gene (EFTUD2) participates in antiviral immune responses. However, the association between genetic polymorphisms of EFTUD2 and hepatitis B virus (HBV) infection susceptibility has not been well-studied. We analyzed the relationship between single nucleotide polymorphisms (SNPs) of EFTUD2 and HBV infection susceptibility and clarified the potential function.
Methods
In total, 448 control subjects and 379 patients with chronic HBV infection from Zhangjiagang First People’s Hospital (Jiangsu, China) were enrolled. Sequenom iPLEX assay was used to detect genotypes of four SNPs (rs1071682, rs2277617, rs2289674, and rs3809756). Dual-luciferase reporter vectors with wild-type A and mutant-type C alleles of EFTUD2 rs3809756 were transfected into HepG2 cells to explore effects on transcription activity.
Results
Only rs3809756 was significantly associated with HBV infection susceptibility (P < .05). The risk of HBV infection was higher in individuals carrying the rs3809756-CC genotype than in those carrying the rs3809756-AA genotype (odds ratio [OR] = 1.945, 95% confidence interval [CI] = 1.129–3.351, P = .017). Subgroup analysis based on the dominant model revealed that rs3809756-AC and rs3809756-CC carriers had a significantly higher risk of HBV infection than rs3809756-AA carriers among patients who were male (OR = 1.732, 95% CI = 1.218–2.464, P = .002), were aged ≥47 years (OR = 1.502, 95% CI = 1.050–2.148, P = .026), or without liver cirrhosis (OR = 1.407, 95% CI = 1.077–1.838, P = .012). In the dual-luciferase reporter assay, the relative luciferase activity of rs3809756-C was significantly lower than that of rs3809756-A (P < .05).
Conclusion
EFTUD2 rs3809756A>C was associated with HBV infection susceptibility and might be involved in the downregulation of promoter activity.
Abbreviations
| ALT | = | alanine aminotransferase |
| ANOVA | = | analysis of variance |
| AST | = | aspartate aminotransferase |
| cccDNA | = | covalently closed circular DNA |
| CHB | = | chronic hepatitis B |
| CI | = | confidence interval |
| HBeAg | = | hepatitis Be antigen |
| HBsAg | = | hepatitis B surface antigen |
| HBV | = | hepatitis B virus |
| HCV | = | hepatitis C virus |
| IFN-α | = | interferon-α |
| IL-6 | = | interleukin 6 |
| IL-10 | = | interleukin 10 |
| IRF3 | = | IFN regulatory factor 3 |
| MAF | = | minor allele frequency |
| MDA5 | = | melanoma differentiation associated protein 5 |
| MVP | = | major vault protein |
| MyD88 | = | myeloid differentiation factor 88 |
| OR | = | odds ratio |
| RIG-1 | = | retinoic acid-inducible gene 1 |
| RLA | = | relative luciferase activity |
| siRNA | = | small interfering RNA |
| SNPs | = | single nucleotide polymorphisms |
| TLR | = | toll-like receptor |
| TNF-α | = | tumor necrosis factor-α |
| UBE2L3 | = | ubiquitin conjugating enzyme E2 L3 |
Disclosure statement
The authors declare that they have no conflict of interest.
Author contributions
Anran Tian: Conceptualization, data curation, formal analysis, investigation, methodology, software, and writing-original draft.
Yuwen Li: Conceptualization, data curation, methodology, resources, software, and writing of original draft.
Haozhi Fan: Conceptualization, data curation, formal analysis, methodology, software, and visualization.
Pingping Hu: Data curation, investigation, validation, and visualization.
Ruirui Xu: Data curation, investigation, validation, and visualization.
Hui Yuan: Formal analysis, investigation, and validation.
Jinyuan Cai: Formal analysis, investigation, and validation.
Wen Zhang: Formal analysis and investigation.
Ming Yue: Conceptualization, project administration, supervision, writing–review and editing.
Jun Li: Conceptualization, project administration, supervision, writing–review and editing.
Chen Dong: Conceptualization, funding acquisition, project administration, supervision, writing–review and editing.
Chuanlong Zhu: Conceptualization, funding acquisition, methodology, project administration, supervision, writing–review and editing.