Prediction of genetic risk for metabolic syndrome

Yamada, Yoshiji; Kato, Koichi; Hibino, Takeshi; Yokoi, Kiyoshi; Matsuo, Hitoshi; Segawa, Tomio; Watanabe, Soichi; Ichihara, Sahoko; Yoshida, Hidemi; Satoh, Kei; Nozawa, Yoshinori

doi:10.1016/j.atherosclerosis.2006.05.035

Cited by 74 publications

(95 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5,30 It does so by reducing hepatic very low-density lipoprotein (VLDL) secretion and increasing VLDL metabolism. 2 There are reports of association of SNPs in the APOA5 gene with cardiovascular disease, including carotid atherosclerosis, 28 stroke 31 and coronary artery disease.…”

Section: Discussionmentioning

confidence: 99%

“…3 Single nucleotide polymorphisms (SNPs) in this gene, such as rs662799 (À1131T4C), have been reported to be associated with hypertriglyceridaemia in Caucasians and Asians. [3][4][5][6] It is not clear if other SNPs in APOA5 might also be related to triglyceride level. Therefore, we investigated the relationship between tagging SNPs in the APOA5 gene with triglyceride level in the Hong Kong Cardiovascular Risk Prevalence Study and confirmed the results in a larger group of subjects from the Guangzhou Biobank Cohort Study.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese

et al. 2010

View full text Add to dashboard Cite

Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5) gene have been associated with hypertriglyceridaemia. We investigated which SNPs in the APOA5 gene were associated with triglyceride levels in two independent Chinese populations. In all, 1375 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study were genotyped for five tagging SNPs chosen from HapMap. Replication was sought in 1996 subjects from the Guangzhou Biobank Cohort Study. Among the five SNPs, rs662799 (-1131T4C) was strongly related to log-transformed triglyceride levels among Hong Kong subjects (b¼0.192, P¼2.6Â10 À13 ). Plasma triglyceride level was 36.1% higher in CC compared to TT genotype. This association was confirmed in Guangzhou subjects (b¼0.159, P¼1.3Â10 À12 ), and was significantly irrespective of sex, age group, obesity, metabolic syndrome, hypertension, diabetes, smoking and alcohol drinking. The odds ratios and 95% confidence interval for plasma triglycerides Z1.7 mmol/l associated with TC and CC genotypes were, respectively, 1.81 (1.37-2.39) and 2.22 (1.44-3.43) in Hong Kong and 1.27 (1.05-1.54) and 1.97 (1.42-2.73) in Guangzhou. Haplotype analysis suggested the association was due to rs662799 only. The corroborative findings in two independent populations indicate that the APOA5-1131T4C polymorphism is an important and clinically relevant determinant of plasma triglyceride levels in the Chinese population.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Genotyping involved PCR amplification, hybridization, streptavidin-phycoerythrin reaction, and measurement of fluorescence. Detailed genotyping methodology was previously described (12,20,21).…”

Section: Methodsmentioning

confidence: 99%

“…We previously showed that the -1131T→C polymorphism (rs662799) of the apolipoprotein A-V gene (APOA5) and the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) were significantly associated with the prevalence of dyslipidemia (10,11) and MetS (12)(13)(14) in Japanese individuals. Given that gene-gene interactions may play important roles in the development of multifactorial complex disorders, we hypothesized that rs662799 of APOA5 and rs6929846 of BTN2A1 may synergistically affect the development of dyslipidemia and MetS.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of genetic variants of APOA5 and BTN2A1 on dyslipidemia or metabolic syndrome

Hiramatsu

Oguri²,

Kato

et al. 2012

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

Abstract. We previously showed that the -1131T→C polymorphism (rs662799) of the apolipoprotein A-V gene (APOA5) and the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) were significantly associated with an increased serum concentration of triglycerides, a decreased serum concentration of high density lipoprotein (HDL)-cholesterol, and the prevalence of metabolic syndrome (MetS) in Japanese individuals. The purpose of the present study was to examine whether these polymorphisms synergistically affect the prevalence of dyslipidemia and MetS in East Asian populations. The study populations comprised 7471 Japanese and 3529 Korean individuals in the dyslipidemia study, and 3474 Japanese and 1671 Korean individuals in the MetS study. Multivariable logistic regression analysis of combined genotypes with adjustment for age, gender and diabetes mellitus revealed that rs662799 and rs6929846 significantly and synergistically affected dyslipidemia. Japanese or Korean individuals with the C allele of APOA5 and the T allele of BTN2A1 had a 2.05-or 1.92-fold increased risk for hypertriglyceridemia and a 1.82-or 1.56-fold increased risk for hypo-HDL-cholesterolemia, respectively, compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Similar analysis with adjustment for age and gender revealed that Japanese individuals, but not Korean individuals, with the C allele of APOA5 and the T allele of BTN2A1 had a 2.87-fold increased risk for MetS compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Genetic variants of APOA5 and BTN2A1 may synergistically affect the prevalence of dyslipidemia in East Asian populations and of MetS in Japanese individuals.

show abstract

“…Transgenic mice expressing human apolipoprotein A-V (apoA-V) have decreased plasma triacylglycerol (TG) 2 levels, whereas APOA5 knock-out mice show increased plasma TG levels. Genetic variation in the human APOA5 locus correlate with changes in plasma lipoprotein levels (2)(3)(4), and a common polymorphism in APOA5 is significantly associated with increased risk for the metabolic syndrome (5,6). Mutations in the APOA5 gene, leading to truncated apoA-V devoid of lipidbinding domains, have been demonstrated to cause severe hyperlipidemia if present in patients in the homozygous state (7).…”

mentioning

confidence: 99%

Endocytosis of Apolipoprotein A-V by Members of the Low Density Lipoprotein Receptor and the Vps10p Domain Receptor Families

Nilsson

Christensen

Raarup

et al. 2008

Journal of Biological Chemistry

104

View full text Add to dashboard Cite

Apolipoprotein A-V (apoA-V) is present in low amounts in plasma and has been found to modulate triacylglycerol levels in humans and in animal models. ApoA-V displays affinity for members of the low density lipoprotein receptor (LDL-R) gene family, known as the classical lipoprotein receptors, including LRP1 and SorLA/LR11. In addition to LDL-A binding repeats, the mosaic receptor SorLA/LR11 also possesses a Vps10p domain. Here we show that apoA-V also binds to sortilin, a receptor from the Vsp10p domain gene family that lacks LDL-A repeats. Binding of apoA-V to sortilin was competed by neurotensin, a ligand that binds specifically to the Vps10p domain. To investigate the biological fate of receptor-bound apoA-V, binding experiments were conducted with cultured human embryonic kidney cells transfected with either SorLA/LR11 or sortilin. Compared with nontransfected cells, apoA-V binding to SorLA/ LR11-and sortilin-expressing cells was markedly enhanced. Internalization experiments, live imaging studies, and fluorescence resonance energy transfer analyses demonstrated that labeled apoA-V was rapidly internalized, co-localized with receptors in early endosomes, and followed the receptors through endosomes to the trans-Golgi network. The observed decrease of fluorescence signal intensity as a function of time during live imaging experiments suggested ligand uncoupling in endosomes with subsequent delivery to lysosomes for degradation. This interpretation was supported by experiments with 125 I-labeled apoA-V, demonstrating clear differences in degradation between transfected and nontransfected cells. We conclude that apoA-V binds to receptors possessing LDL-A repeats and Vsp10p domains and that apoA-V is internalized into cells via these receptors. This could be a mechanism by which apoA-V modulates lipoprotein metabolism in vivo.APOA5 is localized in the apolipoprotein APOA4/APOC3/ APOA1 gene cluster on human chromosome 11q23 (1). Transgenic mice expressing human apolipoprotein A-V (apoA-V) have decreased plasma triacylglycerol (TG) 2 levels, whereas APOA5 knock-out mice show increased plasma TG levels. Genetic variation in the human APOA5 locus correlate with changes in plasma lipoprotein levels (2-4), and a common polymorphism in APOA5 is significantly associated with increased risk for the metabolic syndrome (5, 6). Mutations in the APOA5 gene, leading to truncated apoA-V devoid of lipidbinding domains, have been demonstrated to cause severe hyperlipidemia if present in patients in the homozygous state (7).The mechanism whereby apoA-V exerts its effect on plasma TG levels is unknown. Animal studies and in vitro experiments have given rise to two different hypotheses for the function of apoA-V in vivo, inhibition of VLDL-TG production (8) or modulation of lipoprotein lipase (LPL) activity (8 -11). Adenovirusmediated gene transfer of human apoA-V into apoE-deficient mice decreased plasma TG levels as well as total plasma cholesterol levels without affecting LPL activity (12). In vitro experiments support a role fo...

show abstract

Prediction of genetic risk for metabolic syndrome

Cited by 74 publications

References 33 publications

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese

Synergistic effects of genetic variants of APOA5 and BTN2A1 on dyslipidemia or metabolic syndrome

Endocytosis of Apolipoprotein A-V by Members of the Low Density Lipoprotein Receptor and the Vps10p Domain Receptor Families

Contact Info

Product

Resources

About