Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren

Endo, Kazue; Yanagi, Hisako; Araki, Jungo; Hirano, Chiaki; Yamakawa‐Kobayashi, Kimiko; Tomura, Shigeo

doi:10.1007/s00439-002-0825-0

Cited by 111 publications

(87 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 72%

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The four common SNPs and their association with TG have shown the same effect in Caucasian, 4,7,31 African-American, 5,7 Hispanic, 5 Japanese 31,32 and Chinese 31,32 populations.…”

Section: Snps/haplotypes and Plasma Tg Concentrationmentioning

confidence: 84%

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

2010

View full text Add to dashboard Cite

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.

show abstract

“…Moreover, whereas genetic association studies have revealed consistent association of minor APOA5 alleles with increased plasma TG levels (2,4,5,21,22), the influence of APOA5 polymorphisms on plasma TC levels is less clear. The minor allele of the APOA5 Ϫ1131T3 C promoter variant has been associated with a modest decrease of HDL cholesterol in some but not all studies (21,22) and in one study with a more pronounced increase of VLDL-cholesterol (21). Although apoAV-induced TG reduction thus may be more relevant for human lipid metabolism compared with the TC-reducing effect, the mechanism underlying the effect on HDL is intriguing.…”

Section: Discussionmentioning

confidence: 97%

“…Previously, plasma TC levels were reported to be unaffected by the absence (apoa5 Ϫ/Ϫ mice) or overexpression (human APOA5 transgenic mice) of apoAV (2). Moreover, whereas genetic association studies have revealed consistent association of minor APOA5 alleles with increased plasma TG levels (2,4,5,21,22), the influence of APOA5 polymorphisms on plasma TC levels is less clear. The minor allele of the APOA5 Ϫ1131T3 C promoter variant has been associated with a modest decrease of HDL cholesterol in some but not all studies (21,22) and in one study with a more pronounced increase of VLDL-cholesterol (21).…”

Section: Discussionmentioning

confidence: 99%

ApoAV Reduces Plasma Triglycerides by Inhibiting Very Low Density Lipoprotein-Triglyceride (VLDL-TG) Production and Stimulating Lipoprotein Lipase-mediated VLDL-TG Hydrolysis

Schaap¹,

Rensen

Voshol

et al. 2004

Journal of Biological Chemistry

271

247

View full text Add to dashboard Cite

ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 ؋ 10 8 plaqueforming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29 -37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68 -88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins.Hypertriglyceridemia is a risk factor for coronary heart disease independent from the well known risk factors such as elevated LDL 1 and reduced HDL cholesterol levels (1). Recently, a novel apolipoprotein, apoAV, has been identified that strongly influences plasma triglyceride (TG) levels (2, 3). The human APOA5 gene is part of the apolipoprotein gene cluster on chromosome 11q23 that also encompasses APOA1, APOC3, and APOA4. An initial study revealed the association of three single nucleotide polymorphisms within the APOA5 locus with plasma TG levels and VLDL mass in humans (2). Importantly, these metabolic effects were not associated with a genetic marker in the nearby APOC3 gene that is also known to affect plasma TG levels (2). Subsequent studies in diverse ethnic groups uncovered additional single nucleotide polymorphisms including apoAV protein variants and further supported a role for common genetic variations in APOA5 in influencing plasma TG levels (4, 5). Interestingly, in a recent study, minor allele frequencies of 3 of 5 studied single nucleotide polymorphisms were found to be significantly higher in a hypertriglyceridemic population (4).Mouse models confirmed the TG-modulating effects of apoAV observed in humans. Mice expressing a human APOA5 transgene showed a 65% decrease in plasma TG levels compared with control mice (2). Conversely, apoa5 knock-out mice showed a 400% increase in plasma TG concentration (2). Interestingly, the adenovirus-mediated expression of apoAV in mice resulted in a decrease of b...

show abstract

Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren

Cited by 111 publications

References 11 publications

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

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

ApoAV Reduces Plasma Triglycerides by Inhibiting Very Low Density Lipoprotein-Triglyceride (VLDL-TG) Production and Stimulating Lipoprotein Lipase-mediated VLDL-TG Hydrolysis

Contact Info

Product

Resources

About