Linkage and Association Between Distinct Variants of the
            <i>APOA1/C3/A4/A5</i>
            Gene Cluster and Familial Combined Hyperlipidemia

Eichenbaum‐Voline, Sophie; Olivier, Michael; Jones, Emma; Naoumova, R.P.; Jones, Bradley M.; Gau, Brian; Patel, Hetal; Seed, Mary; Betteridge, D. J.; Galton, D. J.; Rubin, Edward M.; Scott, James; Shoulders, Carol C.; Pennacchio, Len A.

doi:10.1161/01.atv.0000099881.83261.d4

Cited by 94 publications

(81 citation statements)

References 52 publications

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“…However, because there were high correlations between the phenotypes and marker alleles were interdependent, there was no necessity to adjust for multiple comparisons. 5,29,30 In addition, type I errors are random and patterns in results that confirm previous reports should be given more weight than isolated results with a single low P-value. 5,29 Moreover, correction for multiple comparisons largely increases the likelihood of type II errors and important differences are considered nonsignificant.…”

Section: Discussionmentioning

confidence: 51%

Different effects of apolipoprotein A5 SNPs and haplotypes on triglyceride concentration in three ethnic origins

2010

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Several polymorphisms in the ApoA5 gene emerged as important candidate genes in triglyceride metabolism. The aim of this study was to determine the associations between ApoA5 polymorphisms, plasma triglyceride concentrations and the presence of cardiovascular disease (CVD) in three ethnic origins. Genotypes for 15 single nucleotide polymorphisms (SNPs) were determined in 659 older adults (mean age 71 ± 7 years) who immigrated to Israel or whose ancestors originated from East Europe (Ashkenazi), North Africa, Asia (Sephardic) or Yemen (Yemenite). The minor alleles of the four common SNPs (rs662799, rs651821, rs2072560 and rs2266788) are associated with an increase of 27-38% in triglyceride concentration among Ashkenazi and Yemenite Jews compared with the major alleles, but not among those of Sephardic origin. Conversely, among the Sephardic group, the presence of the minor allele in SNP rs3135506 compared with the major allele was associated with an increase of 34% in triglyceride concentration. The four SNPs were in significant linkage disequilibrium (D¢¼0.96-0.99), resulting in three haplotypes H1, H2 and H3, representing 98-99% of the population. Haplotype H2 was significantly associated with triglyceride concentration among Ashkenazi and Yemenite but not among Sephardic Jews. Conversely, haplotype H3 was associated with triglyceride concentration in Sephardic but not in Ashkenazi and Yemenite Jews. Ashkenazi carriers of H2 haplotype had a CVD odds ratio of 2.19 (95% CI: 1.05-4.58) compared with H1 (the most frequent), after adjustment for all other risk factors. These results suggest that different SNPs in ApoA5 polymorphisms may be associated with triglyceride concentration and CVD in each of these ethnic origins.

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Section: Discussionmentioning

confidence: 51%

Different effects of apolipoprotein A5 SNPs and haplotypes on triglyceride concentration in three ethnic origins

2010

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“…Two common haplotypes were defined: APOA5*2 based on −1131C→T and APOA5*3 based on the c56C→G polymorphism [8]. Association studies have shown a positive correlation between plasma triglycerides and the rare variant of the c56C→G, as well as the rare variant of the −1131T→C in a number of different populations, patient cohorts, and ethnic groups [7,12,13,[25][26][27][28][29][30][31][32]. In the present study, the associations between these genetic variations and plasma triglycerides did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 72%

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

et al. 2006

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Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in patients with type 2 diabetes at baseline and during atorvastatin treatment, a lipid-lowering treatment that results in a reduction in plasma triglycerides and APOC3. Subjects, materials and methods: Plasma APOA5 concentration was measured by ELISA in 215 subjects with type 2 diabetes, who were taken from the Diabetes Atorvastatin Lipid-lowering Intervention (DALI) study, a 30-week randomised, double-blind, placebo-controlled study, and given atorvastatin 10 mg or 80 mg daily. Results: At baseline, average plasma APOA5 concentration was 25.7±15.6 μg/100 ml. Plasma APOA5 (R s =0.40), APOC3 (R s =0.72) and APOE (R s =0.45) were positively correlated with plasma triglyceride levels (all p<0.001). In multiple linear regression analysis, adjusted for age and sex, the variation in plasma triglycerides was explained mostly by APOC3 (52%) and only to a small extent by APOA5 (6%) and APOE (1%). Atorvastatin treatment decreased plasma triglycerides, APOA5, APOC3 and APOE (all p<0.0001). After treatment, APOC3 remained the major determinant of plasma triglyceride levels (59%), while the contributions of APOA5 and APOE were insignificant (2 and 3%). Conclusions/interpretation: Our findings reveal a positive association between plasma APOA5 and triglycerides in patients with type 2 diabetes. Treatment with atorvastatin decreased plasma APOA5, APOC3, APOE and triglycerides. In contrast to APOC3, APOA5 is not a major determinant of triglyceride metabolism in these patients.

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“…Our findings, however, suggest that apoAV is not involved in the pathogenesis of the secondary hypertriglyceridaemia associated with obesity and insulin resistance in these rats. In humans with hypertriglyceridaemia or familial combined hyperlipidaemia, polymorphisms in APOA5 show a strong association with plasma triglyceride levels across several ethnic groups [2][3][4]39]. ApoAV deficiency leads to severe hypertriglyceridaemia [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…The gene for apoAV (APOA5) is part of the APOA1/A4/C3/A5 gene cluster on chromosome 11 in man, and APOA5 is predominantly expressed in the liver. Human APOA5 polymorphisms are associated with elevated plasma triglyceride levels [2][3][4]. Studies in genetically modified mice and adenovirus overexpression experiments revealed a strong triglyceride-lowering effect of apoAV [2,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats

Dorfmeister

Brandlhofer

Schaap³

et al. 2006

Diabetologia

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Linkage and Association Between Distinct Variants of the APOA1/C3/A4/A5 Gene Cluster and Familial Combined Hyperlipidemia

Abstract: Objective-Combined hyperlipidemia is a common disorder, characterized by a highly atherogenic lipoprotein profile and a substantially increased risk of coronary heart disease.

Cited by 94 publications

References 52 publications

Different effects of apolipoprotein A5 SNPs and haplotypes on triglyceride concentration in three ethnic origins

Different effects of apolipoprotein A5 SNPs and haplotypes on triglyceride concentration in three ethnic origins

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats

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