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Phosphatidylethanolamine N-methyltransferase gene rs7946 polymorphism plays a role in risk of nonalcoholic fatty liver disease: evidence from meta-analysis

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Phosphatidylethanolamine N-methyltransferase (PEMT) governs the secretion of hepatic triglycerides in the form of very low-density lipoprotein and has been implicated in nonalcoholic fatty liver disease (NAFLD). Studies on the role of the PEMT rs7946 polymorphism as a genetic modifier of NAFLD have reported inconsistent results. This meta-analysis was carried out to evaluate and summarize the association of PEMT rs7946 with susceptibility to NAFLD.


A comprehensive literature search in Scopus, PubMed, Embase, Science Direct and Google Scholar was performed up to 31 August 2015, followed by data extraction and examination of summary estimates.


Six independent studies with a total of 792 NAFLD cases and 2722 controls fulfilled the inclusion criteria. Pooled results indicated that the rs7946 A-allele was associated significantly with an increased risk of NAFLD [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.14–2.11, P=0.005]. A significant association was also found in alternative genetic models of inheritance: dominant, recessive and homozygote (OR 1.62, 95% CI 1.10–2.39, P=0.01; OR 1.42, 95% CI 1.12–1.81, P=0.003; and OR 1.64, 95% CI 1.18–2.29, P=0.004, respectively). Subgroup analysis by ethnicity indicated a significant association only in the East-Asians in the additive (OR=2.08, 95% CI 1.12–3.86, P=0.02), recessive (OR=2.94, 95% CI 1.60–5.37, P=0.0005) and homozygote (OR=1.86, 95% CI 1.15–3.01, P=0.01) models.


This study provides evidence of a significant association between the PEMT rs7946 A-allele and a risk of NAFLD, with the effect being more prominent in East-Asians, but not in non-Asians.
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Keywords: PEMT; fatty liver; genetic variation; meta-analysis; nonalcoholic fatty liver disease; polymorphism; single nucleotide polymorphism

Document Type: Research Article

Affiliations: 1: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya 2: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Publication date: February 1, 2016

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