Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease

Woestijne, Anton P. van de; Graaf, Yolanda van der; Bakker, Paul I. W. de; Asselbergs, Folkert W.; Spiering, Wilko; Visseren, Frank L.J.

doi:10.1371/journal.pone.0101082

Cited by 24 publications

(19 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the contribution of rs964184 to the increased susceptibility to type 2 DM was examined in several GWASs mainly with Caucasians, the significant association was not detected (32,33). The reason for the discrepancy between the previous studies and the present results remains unclear.…”

Section: Discussioncontrasting

confidence: 90%

“…In addition, the prevalence of type 2 DM in the present population was 38.2%, which was more than twice that reported previously (32). The higher frequency of the G allele and the higher prevalence of type 2 DM in the present population compared to those in the previous studies (33,34) may increase the statistical power to detect the association of rs964184 with type 2 DM.…”

Section: Discussionsupporting

confidence: 55%

“…The frequencies of the CG and GG genotypes of rs9645184 were 23.7 and 2.4%, respectively, in Caucasian populations (32), whereas in the present study population they were 39.1 and 7.2%, respectively. The G allele of rs964184 was therefore higher in the present population (26.8%) compared to the Caucasian population (13-14%) (23,33,34). In addition, the prevalence of type 2 DM in the present population was 38.2%, which was more than twice that reported previously (32).…”

Section: Discussioncontrasting

confidence: 45%

See 2 more Smart Citations

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

et al. 2014

View full text Add to dashboard Cite

Abstract.Various loci and genes that confer susceptibility to coronary heart disease (CHD) have been identified in Caucasian populations by genome-wide association studies (GWASs). As type 2 diabetes mellitus (DM) is an important risk factor for CHD, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to CHD through affecting the susceptibility to type 2 DM. The purpose of the present study was to examine a possible association of type 2 DM in Japanese individuals with 29 polymorphisms identified as susceptibility loci for CHD by meta-analyses of the GWASs. The study subjects comprised of 3,757 individuals (1,444 subjects with type 2 DM and 2,313 controls). The polymorphism genotypes were determined by the multiplex bead-based Luminex assay, which combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. To compensate for multiple comparisons of genotypes, the criterion of a false discovery rate (FDR) ≤0.05 was adopted for testing the statistical significance of the association. The comparisons of allele frequencies by the χ 2 test revealed that the rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1) was significantly associated (P=0.0017; FDR=0.050) with type 2 DM. Multivariable logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 was significantly associated (P= 0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minor G allele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed among ZPR1 genotypes with the G allele associated with increases in these parameters. ZPR1 may thus be a susceptibility locus for type 2 DM in Japanese individuals.

show abstract

Section: Discussioncontrasting

confidence: 90%

Section: Discussionsupporting

confidence: 55%

Section: Discussioncontrasting

confidence: 45%

See 1 more Smart Citation

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The encoded APOA1 protein is a cofactor for the lecithin cholesterol acyltransferase, which plays an important role in the cholesterol reverse transport by promoting its efflux from tissue to the liver for excretion. Notably, another gene at the same locus, APOA5, has been previously associated with hTG, and both genes have been concomitantly implicated in the disease (13,(36)(37)(38)(39)(40). Hence, the strong link of this variant to hTG observed in this study unequivocally points to a central role for the APOA1 gene in this disorder.…”

Section: Discussionsupporting

confidence: 65%

A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia

et al. 2017

View full text Add to dashboard Cite

Hypertriglyceridemia (hTG) is a lipid disorder, resulting from an elevation in triglyceride levels, with a strong genetic component. It constitutes a significant risk factor for coronary artery disease (CAD), a leading cause of death worldwide. In this study, we performed a common variant association study for hTG in ethnic Saudi Arabs. We genotyped 5501 individuals in a two-phase experiment using Affymetrix Axiom Genome-Wide CEU 1 Array (Affymetrix, Santa Cruz, CA) that contains a total of 587,352 single nucleotide polymorphisms (SNPs). The lead variant was the rs1558861 [1.99 (1.73-2.30); p = 7.37 × 10 ], residing on chromosome (chr) 11 at the apolipoprotein A-I/A-5 (APOA1/APOA5) locus. The rs780094 [1.34 (1.21-1.49); p = 8.57 × 10 ] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 × 10 ] on chr1 at the laminin subunit gamma-1 (LAMC1) locus showed suggestive association with disease. Furthermore, the rs17145738 [0.68 (0.60-0.77); p = 6.69 × 10 ] on chr7 at the carbohydrate-responsive element-binding protein-encoding (MLXIPL) gene locus displayed significant protective characteristics, while another variant rs6982502 [0.76 (0.68-0.84); p = 5.31 × 10 ] on chr8 showed similar but weaker properties. These findings were replicated in 317 cases vs 1415 controls from the same ethnic Arab population. Our study identified several variants across the human genome that are associated with hTG in ethnic Arabs.

show abstract

“…Unfortunately this attenuated the association with this SNP and it no longer significant, leading to the conclusion that rs964184 is more strongly associated with fasting TG than the PPL TG response. Van de Woestijne et al [43] documented an association between fasting TG and rs964184 among patients with known vascular disease which was modified by the presence of metabolic syndrome. While we were unable to assess this in our population because we did not measure clinical vascular disease, it corroborates the importance of studying lipids in relation to CVD.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

et al. 2015

View full text Add to dashboard Cite

Objective The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Methods The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n=843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n=1,715) was performed on the top SNPs from GOLDN. Results GOLDN revealed 111 suggestive (p<1E-05) associations, with two SNPs meeting GWA significance level (p<5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p=1.20E-03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p=1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG. Conclusion This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics.

show abstract

Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease

Cited by 24 publications

References 20 publications

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia

Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

Contact Info

Product

Resources

About