Common variants APOC3, APOA5, APOE and PON1 are associated with variation in plasma lipoprotein traits in Greenlanders

Lahiry, Piya; Ban, Matthew R.; Pollex, Rebecca L.; Sawyez, Cynthia G.; Huff, Murray W.; Young, T. Kue; Bjerregaard, Peter; Hegele, Robert A.

doi:10.3402/ijch.v66i5.18311

Cited by 17 publications

(9 citation statements)

References 49 publications

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“…Variants in PON1 previously have been associated with serum HDL and LDL cholesterol levels [51,52], and with increased risk for stroke [53]. There have been multiple studies and meta-analyses evaluating the association of PON1 variants with blood lipids in several populations or community-based samples, but with inconsistent results [51,54-61]. …”

Section: Discussionmentioning

confidence: 99%

Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

et al. 2010

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BackgroundThe identification of genetic variants related to blood lipid levels within a large, population-based and nationally representative study might lead to a better understanding of the genetic contribution to serum lipid levels in the major race/ethnic groups in the U.S. population.MethodsUsing data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), we examined associations between 22 polymorphisms in 13 candidate genes and four serum lipids: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). Univariate and multivariable linear regression and within-gene haplotype trend regression were used to test for genetic associations assuming an additive mode of inheritance for each of the three major race/ethnic groups in the United States (non-Hispanic white, non-Hispanic black, and Mexican American).ResultsVariants within APOE (rs7412, rs429358), PON1 (rs854560), ITGB3 (rs5918), and NOS3 (rs2070744) were found to be associated with one or more blood lipids in at least one race/ethnic group in crude and adjusted analyses. In non-Hispanic whites, no individual polymorphisms were associated with any lipid trait. However, the PON1 A-G haplotype was significantly associated with LDL-C and TC. In non-Hispanic blacks, APOE variant rs7412 and haplotype T-T were strongly associated with LDL-C and TC; whereas, rs5918 of ITGB3 was significantly associated with TG. Several variants and haplotypes of three genes were significantly related to lipids in Mexican Americans: PON1 in relation to HDL-C; APOE and NOS3 in relation to LDL-C; and APOE in relation to TC.ConclusionsWe report the significant associations of blood lipids with variants and haplotypes in APOE, ITGB3, NOS3, and PON1 in the three main race/ethnic groups in the U.S. population using a large, nationally representative and population-based sample survey. Results from our study contribute to a growing body of literature identifying key determinants of plasma lipoprotein concentrations and could provide insight into the biological mechanisms underlying serum lipid and cholesterol concentrations.

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Section: Discussionmentioning

confidence: 99%

Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

et al. 2010

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“…Single nucleotide polymorphisms in candidate genes for lipid metabolism are associated with variations in plasma lipoprotein levels in populations with low genetic and environmental variability (11,12). In this sample of Greenland Inuit, plasma levels of the lipids, lipoproteins, and apolipoproteins measured have already been shown to be associated with common variants of genes that show replicable associations with plasma lipid, lipoprotein, and apolipoprotein levels in other populations (12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

Rajakumar

Ban

Cao

et al. 2009

Journal of Lipid Research

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“…Few variants of the PON1 gene was commonly investigated for their association with serum lipid traits. These variants include rs662 (Q192R), rs854560 (L55 M) and rs705379 which showed the association with TC, HDL-C and LDL-C in different populations worldwide [215–219]. However none of the GWAS conducted to date has identified the association of the polymorphism at this locus with serum lipid traits.…”

Section: Genetic Basis Of Polygenic Hypercholesterolemia – the Genes mentioning

confidence: 99%

Genetic determinants of inherited susceptibility to hypercholesterolemia – a comprehensive literature review

2017

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Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. This indicates the probability of having other genes with a causative or contributory role in the pathogenesis of hypercholesterolemia and suggests a polygenic inheritance of this condition. Here in, we review the recent evidence of association of the genetic variants with hypercholesterolemia and the three lipid traits; total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C), their biological pathways and the associated pathogenetic mechanisms. Nearly 80 genes involved in lipid metabolism (encoding structural components of lipoproteins, lipoprotein receptors and related proteins, enzymes, lipid transporters, lipid transfer proteins, and activators or inhibitors of protein function and gene transcription) with single nucleotide variants (SNVs) that are recognized to be associated with hypercholesterolemia and serum lipid traits in genome-wide association studies and candidate gene studies were identified. In addition, genome-wide association studies in different populations have identified SNVs associated with TC, HDL-C and LDL-C in nearly 120 genes within or in the vicinity of the genes that are not known to be involved in lipid metabolism. Over 90% of the SNVs in both these groups are located outside the coding regions of the genes. These findings indicates that there might be a considerable number of unrecognized processes and mechanisms of lipid homeostasis, which when disrupted, would lead to hypercholesterolemia. Knowledge of these molecular pathways will enable the discovery of novel treatment and preventive methods as well as identify the biochemical and molecular markers for the risk prediction and early detection of this common, yet potentially debilitating condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0488-4) contains supplementary material, which is available to authorized users.

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Common variants APOC3, APOA5, APOE and PON1 are associated with variation in plasma lipoprotein traits in Greenlanders

Cited by 17 publications

References 49 publications

Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

Genetic determinants of inherited susceptibility to hypercholesterolemia – a comprehensive literature review

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