Association between APOC3 polymorphisms and non-alcoholic fatty liver disease risk: a meta-analysis

Background and Aim: The apolipoprotein C3 (APOC3) polymorphism has been reported to predispose to non-alcoholic fatty liver disease (NAFLD). However, the results remain inconclusive. This meta-analysis aimed to provide insights into the association between APOC3 polymorphisms and NAFLD risk. Methods: Studies with terms “NALFD” and “APOC3” were retrieved from PubMed, Web of Science, CNKI and Wan- fang databases up to August 1, 2019. Pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association of APOC3 polymorphisms and NAFLD risk were calculated using fixed and random-effects models. Results: A total of twelve studies from eleven articles were included. Of them, eight studies (1750 cases and 2181 controls) reported the strong association of variant rs2854116 with NAFLD and six studies (1523 cases and 1568 controls) found the association of rs2854117 polymorphism with NAFLD. Overall, a statistically significant association between rs2854116 pol- ymorphism of APOC3 gene and NAFLD risk was found only under dominant model. However, association of rs2854117 polymorphism with NAFLD risk was not detected under all four genetic models. In sub-group analysis of NAFLD subjects based on country, no association among them in China was detected. Besides, four studies analyze the association between the two polymorphisms and clinical characteristics in all subjects or NAFLD patients, and we also failed detect any associa- tion between the wild carriers and variant carriers. Conclusion: The meta-analyses suggests that the rs2854116 polymorphism but not rs2854117 polymorphism in APOC3 gene might be a risk factor for NAFLD among Asians. That is, individuals with CT+CC genotype have higher risk of devel- oping NAFLD. However, studies with sufficient sample size are needed for the further validation. Keywords: Apolipoprotein C3; polymorphism; non-alcoholic fatty liver disease; meta-analysis.

Sequence analysis and variant identification at the APOC3 gene locus indicates association of rs5218 with BMI in a sample of Kuwaiti’s

Background APOC3 is important in lipid transport and metabolism with limited studies reporting genetic sequence variations in specific ethnic groups. The present study aimed to analyze the full APOC3 sequence among Kuwaiti Arabs and test the association of selected variants with lipid levels and BMI. Methods Variants were identified by Sanger sequencing the entire APOC3 gene in 100 Kuwaiti Arabs. Variants and their genotypes were fully characterized and used to construct haplotype blocks. Four variants (rs5128, rs2854117, rs2070668, KUAPOC3N3 g.5196 A > G) were selected for testing association with serum lipid levels and BMI in a cohort (n = 733). Results APOC3 sequence (4.3 kb) of a Kuwaiti Arab was deposited in Genbank (accession number KJ437193). Forty-two variants including 3 novels were identified including an “A” insertion at genomic positions 116,700,599–116,700,600 (promoter region) and two substitutions in intron 1 at genomic positions 116,700,819 and 116,701,159. Only three variants, (rs5128, rs2854117, and rs2070668) were analyzed for association of which rs5128 showed a trend for association with increased BMI, TG and VLDL levels that was further investigated using multivariate analysis. A significant association of rs5128 with BMI (p < 0.05) was observed following a dominant genetic model with increased risk by an OR of 4.022 (CI: 1.13–14.30). Conclusion The present study is the first to report sequence analysis of APOC3 in an Arab ethnic group. This study supports the inclusion of rs5128 as a marker for assessing genetic risk to dyslipidemia and obesity and the inclusion of the novel variant g.5196 A > G for population stratification of Arabs.

P829The impact of APOC3 and APOE gene polymorphisms on response to statin therapy in acute myocardial infarction

Background and aim Many genetic studies have been reported about the association between APOE, APOC3 gene polymorphisms and response to statin therapy in myocardial infarction, but results remain controversial. The aim of this study was to investigate the association between SNP rs7412 (APOE), rs2854117 (APOC3), rs2854116 (APOC3) and lipid-lowering effect of atorvastatin and rosuvastatin in patients with myocardial infarction. Methods Polymorphism of genes APOE (rs7412), APOC3 (rs2854117 and rs2854116) was determened. Lipid profile was determined on admission and after 1 year of treatment. Results 78 patients with myocardial infarction treated with maximal tolerated dose of atorvastatin or rosuvastatin were included. More pronounced reduction of lipid levels was associated with of T allele of rs7412 (APOE), p<0,05. ANOVA demonstrated greater low-density lipoprotein and total cholesterol decrease in patients with combination of genes CT/TT (rs7412, APOE) and CC (rs2854117, APOC3) genotypes, CT/TT (rs7412, APOE) and CT (rs2854116, APOC3) genotypes. Conclusion The genetic variants of APOC3 and APOE are useful markers and can be use to predict response to lipid-lowering therapy with statin in myocardial infarction.