Roles of cytochrome P4502E1 gene polymorphisms and the risks of alcoholic liver disease: a meta-analysis

Abstract

Background: Previous studies investigating the association between cytochrome P4502E1 (CYP2E1) polymorphisms and the risk of alcoholic liver diseases (ALD) have yielded conflicting results. Thus, a meta-analysis was performed to clarify the association between CYP2E1 polymorphisms and the risks of ALD.

Methods: A comprehensive literature search was conducted to identify the relevant studies. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using Begg's funnel plots and Egger's regression test.

Results: A total of 27 and 9 studies were finally included for the association between the CYP2E1 Pst I/Rsa I or Dra I polymorphisms and the risks of ALD, respectively. Overall, the combined results showed that homozygous genotype c2c2 was significantly associated with increase risk of ALD in worldwide populations (c2c2 vs. c1c1: OR = 3.12, 95%CI 1.91-5.11) when ALD patients were compared with alcoholics without ALD. Significant associations between CYP2E1 Pst I/Rsa I polymorphism and ALD risk were also observed in Asians (c2c2 vs. c1c1: OR = 4.11, 95%CI 2.32-7.29) and in Caucasians (c2c2/c1c2 vs. c1c1: OR = 1.58, 95%CI 1.04-2.42) when ALD patients were compared with alcoholics without ALD. However, subgroup analysis stratified by ALD types showed that CYP2E1 Pst I/Rsa I polymorphism was not significantly associated with the risks of alcoholic cirrhosis (ALC). No significant association was observed between CYP2E1 Dra I polymorphism and ALD risks.

Conclusion: This meta-analysis suggested that CYP2E1 Pst I/Rsa I polymorphism might be not significantly associated with advanced form of ALD (ALC), but might be significantly associated with other form of ALD such as steatosis, hepatisis, fibrosis. Furthermore, CYP2E1 Dra I polymorphism might be not significantly associated with the ALD risks. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.

Figure 1. Flow chart of study selection based on the inclusion and exclusion criteria.

Figure 2. Meta-analysis for CYP2E1 Pst I/Rsa I polymorphism and the risk of ALD (allele c2 vs. c1).

(a) ALD patients vs. alcoholics without ALD; (b) ALD patients vs. non-alcoholics. Each study was shown by a point estimate of the effect size (OR) (size inversely proportional to its variance) and its 95% confidence interval (95%CI) (horizontal lines). The white diamond denotes the pooled OR.

Figure 3. Frequencies of the minor allele (c2 allele) of the CYP2E1 Pst I/Rsa I polymorphism among control subjects stratified by ethnicity.

Figure 4. Meta-analysis for CYP2E1 Dra I polymorphism and the risk of ALD in Caucasians (d1 vs. d2).

(a) ALD patients vs. alcoholics without ALD; (b) ALD patients vs. non-alcoholics. Each study was shown by a point estimate of the effect size (OR) (size inversely proportional to its variance) and its 95% confidence interval (95%CI) (horizontal lines). The white diamond denotes the pooled OR.