APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica

Abstract

Apolipoprotein C-III (apoC-III) and A-V (apoA-V) regulate triglyceride metabolism in opposite ways (1-3). In mice, the overexpression of the human APOC3 transgene (1) leads to severe hypertriglyceridemia, whereas knockout mice lacking the endogenous Apoc3 gene have hypotriglyceridemia (2). In contrast, overexpression of the human APOA5 transgene and the lack of the endogenous Apoa5 gene show opposite triglyceride effects (3).Several studies indicate that naturally occurring sequence variation in the APOC3 and APOA5 genes affects plasma triglyceride concentrations in humans (4-7). People with the G allele of the 3238C Ͼ G polymorphism ( SstI site) in the 3 Ј untranslated region (3 Ј UTR) of APOC3 tend to have higher plasma triglyceride concentrations (4, 5

Apolipoprotein A5 Gene IVS3+G476A Allelic Variant Confers Susceptibility for Development of Ischemic Stroke

“…Our finding is in agreement with those of others using different study populations; bearing these allelic variants has been shown to have obligatory associations with increased triglyceride levels, independent of geographic origin or disease of the population examined. [29][30][31][32] We also compared the serum cholesterol levels in all groups, but we could not detect an association between carrying any allele and cholesterol level, which is consistent with the observations of others; 11,33 however, in some studies, changes in cholesterol levels were observed in carriers of the -1131C allele. 34,35 In the present stroke patients, there was an approximately 2-fold accumulation in the -1131C as well as in the IVS3+ 476A alleles, whereas the distribution of the 1259C allele was almost the same in patients with stroke and in controls.…”

“…These variants have been investigated in relation to their possible modifying effect on lipid metabolism and in relation to their possible impact on the development of cardio-and cerebrovascular diseases. 11,12,28,29 In the present study the possible relationships between the presence of the 1259C and IVS3+476A alleles and the development of ischemic stroke were examined in a stratified stroke population, for the first time in the literature. Besides this, the study design enabled us to also investigate the allele distribution of the T-1131C variants, which had been found to confer risk for the disease in our previous study.…”

Apolipoprotein A5 IVS3+476A Allelic Variant Associates With Increased Trigliceride Levels and Confers Risk for Development of Metabolic Syndrome in Hungarians

“…8,29,32,33 Two SNPs (T-455C and C-482T) in the distal promoter region of APOC3 were found to be associated with reduced affinity for the nuclear transcription factors mediating the downregulating response to insulin. 9,10,33,34 The 2 SNPs of APOA5 are in different linkage with other SNPs of the APOAI-CIII-AIV gene cluster.…”

“…4,7,8,27,28 Studies of Europeans and Middle-Americans have found relationships between serum triglycerides and the abovementioned APOA5 variants, but they did not support that SNPs of APOA5 independently confer risk for coronary artery diseases. 9,29,30 Moreover, the T-1131C allelic variant of APOA5 was recently reported to be associated with the metabolic syndrome in Japanese and Romanian populations. 4,11 The aim of the current study was to investigate the effect of the IVS3+476A and 1259C variants on triglyceride metabolism, and to extend the observations as a case -control association study for these SNPs to investigate their relationship with development of metabolic syndrome.…”

Significant association of APOA5 and APOC3 gene polymorphisms with meat quality traits in Kele pigs

“…In contrast, the expression level of APOC3 is positively correlated with serum TG concentration (Ito et al, 1990;Maeda et al, 1994). Furthermore, polymorphisms of these two genes have been reported to affect lipid deposition (Ruiz-Narváez et al, 2005;Zhang et al, 2010). Therefore, both APOA5 and APOC3 should be promising candidate genes for improving IMF in pigs.…”