Roles of Cytochrome P4502E1 Gene Polymorphisms and the Risks of Alcoholic Liver Disease: A Meta-Analysis

Abstract

BackgroundPrevious 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.MethodsA 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.ResultsA 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.ConclusionThis 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.

Roles of ApoB-100 Gene Polymorphisms and the Risks of Gallstones and Gallbladder Cancer: A Meta-Analysis

“…The significance of the pooled effect size was determined by the Z test. Heterogeneity among the studies was assessed using the Q test and the I 2 test as performed in other studies [27], [28]. The DerSimonian and Laird random effects model was used as the pooling method when significant heterogeneity existed; otherwise, the Mantel-Haenszel fixed effect model was used [29].…”

Genetic Basis of Alcoholic and Nonalcoholic Fatty Liver Disease

“…Cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) localizes to the endoplasmic reticulum and is induced by ethanol; thus the enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal as well as exogenous substrates. A recent meta-analysis showed that CYP2E1 might be signifi cantly associated with the development of steatosis, hepatitis, and fi brosis in patients with AFLD [ 63 ]. It is worth mentioning that there are no published GWAS in AFLD, though two efforts are ongoing-one is a multinational GWAS of alcoholic cirrhosis and another is a US-based GWAS of acute alcoholic hepatitis.…”

Polymorphic Variants of Cytochrome P450

“…In particular, rs2031920 (CYP2E1*5) has been well studied as a risk factor for development of alcoholic liver disease with a number of reports of positive associations together with a recent meta-analysis (Zeng et al, 2013). The basis for the association may involve either higher levels of acetaldehyde being produced from ethanol by CYP2E1 in those positive for rs2031920 if, as discussed in Section 2.1.4, the variant is associated with higher levels of transcription.…”

“…It is also possible that higher levels of reactive oxygen species occur in those positive for the variant since CYP2E1-mediated reactions generate these species (Koop, 1992). The meta-analysis is a useful summary of all studies on the association of rs2031920 with alcoholic liver disease (Zeng et al, 2013). The overall analysis failed to show an overall significant association for carriage of the variant but the study highlights the small size of most published studies with 21 of the 27 considered involving fewer than 100 alcoholic liver disease cases.…”