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Association between rs738409 polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hepatocellular carcinoma susceptibility: Evidence from case-control studies.
Gene. 2019 Feb 15; 685:143-148.GENE

Abstract

OBJECTIVES

Numerous studies have investigated the association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 C > G polymorphism and the risk of hepatocellular carcinoma (HCC). However, the results are conflicting and inconclusive among different populations. Thus, a meta-analysis was performed to resolve this inconsistency.

METHODS

Potentially related studies were investigated in PubMed, Cochrane Library, EMBASE, and Chinese Biomedical Database (CBM) up to June 12, 2018. The odds ratio (OR) with a 95% confidence interval (CI) was used to explore the strength of the associations. Subgroup analysis was performed according to ethnicity and etiology of cases. Publication bias detection was conducted using Egger's test.

RESULTS

Fourteen case-control studies were included in this meta-analysis, reporting a total of 3527 HCC patients and 7184 controls. Overall results revealed that PNPLA3 rs738409 C > G polymorphism was associated with an increased risk of HCC in the populations studied with various types of etiology under allelic model (OR = 1.59, 95%CI: 1.20-2.10, P = 0.001), dominant model (OR = 1.55, 95%CI: 1.13-2.13, P = 0.007), homozygous model (OR = 2.76, 95%CI: 1.52-5.01, P = 0.001), heterozygous model (OR = 1.31, 95%CI: 1.01-1.69, P = 0.039), and recessive model (OR = 2.42, 95%CI: 1.51-3.87, P < 0.001). A significant increased risk was observed in patients with HCC related to alcoholic cirrhosis under all genetic models (C vs. G: OR = 3.35, 95%CI: 2.14-5.24, P < 0.001; CC vs.GG: OR = 11.02, 95%CI: 4.35-27.88, P < 0.001; CC vs. GC: OR = 2.75, 95%CI: 1.72-4.39, P < 0.001; GG vs. CC + CG: OR = 5.82, 95%CI: 2.93-11.57, P < 0.001; CG + GG vs. CC: OR = 4.08, 95%CI: 2.33-7.13, P < 0.001), with respect to specific etiology of HCC. A significant increased risk was also revealed in patients with HCC due to virus related cirrhosis under allelic model (OR = 1.19, 95%CI: 1.07-1.32, P = 0.001), dominant model (OR = 1.17, 95%CI: 1.02-1.35, P = 0.03), homozygous model (OR = 1.47, 95%CI: 1.17-1.85, P = 0.001), and recessive model (OR = 1.43, 95%CI: 1.15-1.76, P = 0.001). Subgroup analysis on ethnicity revealed that the polymorphism was associated with increased risk of HCC in Caucasians under allelic model (OR = 1.65, 95%CI: 1.12-2.45, P = 0.012), dominant model (OR = 1.63, 95%CI: 1.04-4.25, P = 0.035), homozygous model (OR = 2.88, 95%CI: 1.27-6.55, P = 0.012), and recessive model (OR = 2.48, 95%CI: 1.32-4.65, P = 0.005).

CONCLUSIONS

Our study suggests a significant increased association between PNPLA3 rs738409 C > G polymorphism and HCC risk in the entire populations studied, especially in Caucasians. Therefore, PNPLA3 rs738409 C > G polymorphism may be a risk factor for virus and alcoholic-related HCC.

Authors+Show Affiliations

Department of General Surgery, The First People's Hospital of Wenling, Weiling 317500, PR China.Department of General Surgery, The First People's Hospital of Wenling, Weiling 317500, PR China.Department of General Surgery, The First People's Hospital of Wenling, Weiling 317500, PR China. Electronic address: 18357662909@139.com.

Pub Type(s)

Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

30403964

Citation

Li, Jian-Feng, et al. "Association Between Rs738409 Polymorphism in Patatin-like Phospholipase Domain-containing Protein 3 (PNPLA3) Gene and Hepatocellular Carcinoma Susceptibility: Evidence From Case-control Studies." Gene, vol. 685, 2019, pp. 143-148.
Li JF, Zheng EQ, Xie M. Association between rs738409 polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hepatocellular carcinoma susceptibility: Evidence from case-control studies. Gene. 2019;685:143-148.
Li, J. F., Zheng, E. Q., & Xie, M. (2019). Association between rs738409 polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hepatocellular carcinoma susceptibility: Evidence from case-control studies. Gene, 685, 143-148. https://doi.org/10.1016/j.gene.2018.11.012
Li JF, Zheng EQ, Xie M. Association Between Rs738409 Polymorphism in Patatin-like Phospholipase Domain-containing Protein 3 (PNPLA3) Gene and Hepatocellular Carcinoma Susceptibility: Evidence From Case-control Studies. Gene. 2019 Feb 15;685:143-148. PubMed PMID: 30403964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between rs738409 polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hepatocellular carcinoma susceptibility: Evidence from case-control studies. AU - Li,Jian-Feng, AU - Zheng,En-Qi, AU - Xie,Ming, Y1 - 2018/11/04/ PY - 2018/08/15/received PY - 2018/10/29/revised PY - 2018/11/03/accepted PY - 2018/11/8/pubmed PY - 2019/1/2/medline PY - 2018/11/8/entrez KW - Hepatocellular carcinoma KW - Meta-analysis KW - PNPLA3 KW - Single nucleotide polymorphism KW - rs738409 SP - 143 EP - 148 JF - Gene JO - Gene VL - 685 N2 - OBJECTIVES: Numerous studies have investigated the association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 C > G polymorphism and the risk of hepatocellular carcinoma (HCC). However, the results are conflicting and inconclusive among different populations. Thus, a meta-analysis was performed to resolve this inconsistency. METHODS: Potentially related studies were investigated in PubMed, Cochrane Library, EMBASE, and Chinese Biomedical Database (CBM) up to June 12, 2018. The odds ratio (OR) with a 95% confidence interval (CI) was used to explore the strength of the associations. Subgroup analysis was performed according to ethnicity and etiology of cases. Publication bias detection was conducted using Egger's test. RESULTS: Fourteen case-control studies were included in this meta-analysis, reporting a total of 3527 HCC patients and 7184 controls. Overall results revealed that PNPLA3 rs738409 C > G polymorphism was associated with an increased risk of HCC in the populations studied with various types of etiology under allelic model (OR = 1.59, 95%CI: 1.20-2.10, P = 0.001), dominant model (OR = 1.55, 95%CI: 1.13-2.13, P = 0.007), homozygous model (OR = 2.76, 95%CI: 1.52-5.01, P = 0.001), heterozygous model (OR = 1.31, 95%CI: 1.01-1.69, P = 0.039), and recessive model (OR = 2.42, 95%CI: 1.51-3.87, P < 0.001). A significant increased risk was observed in patients with HCC related to alcoholic cirrhosis under all genetic models (C vs. G: OR = 3.35, 95%CI: 2.14-5.24, P < 0.001; CC vs.GG: OR = 11.02, 95%CI: 4.35-27.88, P < 0.001; CC vs. GC: OR = 2.75, 95%CI: 1.72-4.39, P < 0.001; GG vs. CC + CG: OR = 5.82, 95%CI: 2.93-11.57, P < 0.001; CG + GG vs. CC: OR = 4.08, 95%CI: 2.33-7.13, P < 0.001), with respect to specific etiology of HCC. A significant increased risk was also revealed in patients with HCC due to virus related cirrhosis under allelic model (OR = 1.19, 95%CI: 1.07-1.32, P = 0.001), dominant model (OR = 1.17, 95%CI: 1.02-1.35, P = 0.03), homozygous model (OR = 1.47, 95%CI: 1.17-1.85, P = 0.001), and recessive model (OR = 1.43, 95%CI: 1.15-1.76, P = 0.001). Subgroup analysis on ethnicity revealed that the polymorphism was associated with increased risk of HCC in Caucasians under allelic model (OR = 1.65, 95%CI: 1.12-2.45, P = 0.012), dominant model (OR = 1.63, 95%CI: 1.04-4.25, P = 0.035), homozygous model (OR = 2.88, 95%CI: 1.27-6.55, P = 0.012), and recessive model (OR = 2.48, 95%CI: 1.32-4.65, P = 0.005). CONCLUSIONS: Our study suggests a significant increased association between PNPLA3 rs738409 C > G polymorphism and HCC risk in the entire populations studied, especially in Caucasians. Therefore, PNPLA3 rs738409 C > G polymorphism may be a risk factor for virus and alcoholic-related HCC. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/30403964/Association_between_rs738409_polymorphism_in_patatin_like_phospholipase_domain_containing_protein_3__PNPLA3__gene_and_hepatocellular_carcinoma_susceptibility:_Evidence_from_case_control_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(18)31155-7 DB - PRIME DP - Unbound Medicine ER -