Association of ?2-HS glycoprotein (AHSG, fetuin-A) polymorphism with AHSG and phosphate serum levels

Osawa, Motoki; Tian, Wei; Horiuchi, Hidekazu; Kaneko, Mika K.; Umetsu, Kazuo

doi:10.1007/s00439-004-1222-7

Cited by 52 publications

(50 citation statements)

References 36 publications

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“…Analysis of the fetuin-A polymorphisms c.742CϾT (p.T248M) and c.766CϾG (p.T256S) in PXE patients, relatives, and healthy controls revealed 3 genotypes, as reported previously (40 ). Fetuin-A genotype 1 is characterized by the alleles c.742C and c.766C, whereas the fetuin-A genotypes 2-1 and 2 have a C3 T transversion at position 742 and a C3 G transition at position 766 in the heterozygous and homozygous states, respectively (Table …”

Section: Analysis Of the Fetuin-a Genotypesupporting

confidence: 86%

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Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum

et al. 2006

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Section: Analysis Of the Fetuin-a Genotypesupporting

confidence: 86%

“…Low amounts of fetuin-A are associated with extraosseus, in particular, vascular calcification (36,38,39 ). Specific polymorphisms of the fetuin-A gene were demonstrated to influence circulating fetuin-A concentrations (40 ).…”

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confidence: 99%

Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum

et al. 2006

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“…29 Single-nucleotide polymorphisms of the gene encoding AHSG were also shown to affect the serum levels of the protein in different populations. 30,31 Furthermore, an increased consumption was also supposed to result in reduced serum AHSG levels in patients with hematological malignancies. 32 In pregnancy, the fetoplacental unit can be another source of the protein.…”

Section: Discussionmentioning

confidence: 99%

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

et al. 2009

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The purpose of this study was to determine serum a 2 -HS glycoprotein (AHSG) concentration and its diagnostic accuracy in preeclampsia. In this case-control study, the serum C-reactive protein (CRP) and AHSG levels were measured in 93 preeclamptic patients and in 127 healthy pregnant women by immunoturbidimetry and radial immunodiffusion. The serum CRP levels were significantly higher, whereas the serum AHSG concentrations were significantly lower in the preeclamptic group than in the control group (median (25th to 75th percentile), CRP: 6.71 mg l À1 (2.76-12.69) vs. 3.38 mg l À1 (1.69-7.27), respectively; AHSG: 660 lg ml À1 (612-768) vs. 744 lg ml À1 (660-816), respectively; Po0.001 for both). In preeclamptic patients, the serum AHSG concentrations showed significant inverse correlations with systolic blood pressure and serum CRP levels. A low serum AHSG level (p720 lg ml À1 ) was significantly associated with preeclampsia (adjusted odds ratio (95% confidence interval): 3.69 (1.82-7.51); Po0.001). According to the receiver operating characteristic curves, the measurement of serum AHSG concentrations was as accurate as that of serum CRP levels to detect preeclampsia. In conclusion, serum AHSG concentration is decreased and reflects-at least partly-systemic inflammation in preeclampsia.

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“…Homeostasis model assessment of insulin resistance was calculated as fasting plasma glucose (mmol/l) multiplied by fasting serum insulin (pmol/l) and divided by 22.5. acid substitution that has been shown to be functional in the sense that the two minor alleles result in lower in vivo serum levels of AHSG (13). The protein acts in phosphorylation of the insulin receptor tyrosine kinase (1) and has been associated with insulin resistance (4); thus, the observed nominal association in our study of Thr248Met with reduced fasting insulin and insulin resistance may provide a possible explanation of the mechanism by which AHSG variation modulates various metabolic phenotypes such as type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Three polymorphisms (Ϫ843AϾT/rs2248690, Ϫ469TϾG/rs2077119, and Thr248Met/rs4917) were associated with plasma cholesterol among 291 Swedish women for whom a relationship of Ϫ469TϾG with insulin-mediated inhibition of lipolysis was also shown (12). Thr248Met and Thr256Ser (rs4918), which are in almost perfect linkage disequilibrium (LD), were examined among 176 Japanese subjects in relation to serum concentrations of AHSG, which proved to be largely dependent on AHSG Thr248Met and Thr256Ser genotypes (13). Both of these single nucleotide polymorphisms (SNPs) are in almost perfect LD with a third variant, IVS1-903AϾG (rs2593813), which was associated with overweight/obesity among 504 Swedish men, alone and in a haplotype combination with Thr248Met and Thr256Ser (14).…”

Section: Research Design and Methods-mentioning

confidence: 99%

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

et al. 2008

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OBJECTIVE-The gene encoding the ␣2 Heremans-Schmid glycoprotein (AHSG) is a credible biological and positional candidate gene for type 2 diabetes and the metabolic syndrome, and previous attempts to relate AHSG variation with type 2 diabetes and obesity in Swedish and French Caucasians have been largely successful. We related seven frequent AHSG tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia. RESEARCH DESIGN AND METHODS-The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, providing a statistical power of Ͼ99% to replicate previous findings. Data were analyzed in case-control and haplotype settings, and quantitative metabolic traits were examined for association. Moreover, epistatic effects between AHSG variants and insulin receptor substrate-1 (IRS1) and ␤-2-adrenergic receptor polymorphisms were investigated.RESULTS-The Ϫ469TϾG (rs2077119) and IVS6ϩ98CϾT (rs2518136) polymorphisms were associated with type 2 diabetes (P ϭ 0.007 and P ϭ 0.006, respectively, or P corr ϭ 0.04 and P corr ϭ 0.03, respectively, following correction for multiple hypothesis testing), and in a combined analysis of the present and a previous study Ϫ469TϾG remained significant (odds ratio 0.90 [95% CI 0.84 -0.97]; P ϭ 0.007). Furthermore, two AHSG haplotypes were associated with dyslipidemia (P ϭ 0.003 and P corr ϭ 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-oral glucose tolerance test serum insulin release (P ϭ 0.02, P corr ϭ 0.1 for fasting and P ϭ 0.04, P corr ϭ 0.2 for area under the insulin curve) and improved insulin sensitivity estimated by the homeostasis model assessment of insulin resistance (9.0 vs. 8.6 mmol ⅐ l Ϫ1 ⅐ pmol Ϫ1 ⅐ l Ϫ1 ; P ϭ 0.01, P corr ϭ 0.06). Indications of epistatic effects of AHSG variants with the IRS1 Gly971Arg polymorphism were observed for fasting serum triglyceride concentrations.CONCLUSIONS-Based on present and previous findings, common variation in AHSG may contribute to the interindividual variation in metabolic traits. Diabetes 57:1427-1432, 2008 T he ␣ 2 Heremans-Schmid glycoprotein (AHSG) is secreted mainly by the liver and is abundant in plasma. AHSG inhibits insulin-stimulated insulin receptor autophosphorylation, insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS1), and the association of IRS1 with the p85 subunit of phosphatidylinositol-3 kinase in vitro (1-3). Elevated plasma AHSG was associated with insulin resistance in humans (4), and AHSG levels were higher in subjects with impaired glucose tolerance (5) and women with gestational diabetes (6). Ahsg knockout mice demonstrate increased basal and insulin-stimulated insulin receptor phosphorylation, increased glucose clearance, and insulin sensitivity (7). Moreover, even on a high-fat diet and at old age Ahsg knockout mice were resistant to weight gain and remained insulin sens...

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Association of ?2-HS glycoprotein (AHSG, fetuin-A) polymorphism with AHSG and phosphate serum levels

Cited by 52 publications

References 36 publications

Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum

Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

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