Disease relevance of AHSG

• Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia [1].
• Compared to controls, patients with chronic hepatitis C had significantly lower OROSO and CRP, and higher AHSG levels [2].
• AIMS/HYPOTHESIS: The aim of this study was to investigate the effect of single-nucleotide polymorphisms (SNPs) in the gene encoding the human alpha(2)-Heremans-Schmid glycoprotein (AHSG) on obesity and insulin action in adipocytes [3].
• We conclude that a common variation (Thr230Met) in the AHSG gene is associated with a marked increase in beta2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation [4].
• We genotyped 356 overweight or obese (BMI: 37.2 [25.0-66.5] kg/m(2)) and 148 lean (BMI: 23.7 [23.4-24.9] kg/m(2)) otherwise healthy Swedish men for three non-synonymous single-nucleotide polymorphisms (SNPs) within exon 6 (rs4917) and exon 7 (rs4918 and Arg299Cys) and one SNP in intron 1 (rs2593813) of the AHSG gene [5].
• Substantial weight loss in 21 children led to a significant decrease of fetuin-A and the prevalence of NAFLD in contrast to the 15 children without substantial weight loss [6].

Psychiatry related information on AHSG

• The purpose of this study was to investigate the distribution of AHSG gene polymorphism in 235 Caucasian Italian patients with late-onset Alzheimer's disease (LOAD) and 235 age- and gender-matched healthy controls [7].

High impact information on AHSG

• METHODS: We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months [1].
• Fetuin-A (alpha2-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response [1].
• Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO4 precipitation (mean IC50: 9.0 microL serum [SD 3.1] vs 7.5 [0.8] in short-term patients and 6.4 [2.6] in controls) [1].
• In the present study, we have examined the chemotactic response of human peripheral blood monocytes and related polymorphonuclear leucocytes to three constituents of bone matrix: peptides from Type I collagen, alpha 2-HS glycoprotein, and osteocalcin (bone gla protein) [8].
• The AHSG cDNA was utilized for mapping the AHSG gene to the 3q21----qter region of human chromosome 3 [9].

Chemical compound and disease context of AHSG

• Young children, those with previous AHS bacteremias, and those receiving high-dose cytarabine are at particularly high risk of AHS bacteremia [10].
• Given the widespread use of metolachlor and the frequent detection of metolachlor in both surface and ground water, future analyses of the AHS will allow further examination of long-term health effects, including lung cancer and the less common cancers [11].
• We suggest that alpha-2-HS-glycoprotein may act as an inhibitor of the cysteine proteinases responsible for bone resorption [12].
• Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21) [13].
• However, in patients treated with amoxicillin, a significant decline in the number of AHS, and an increase (in Staphylococcus aureus) or no change in the number of other beta-lactamase-producing bacteria (BLPB) was noted [14].

Biological context of AHSG

• DNA sequence analysis reveals identity with the mRNA product of a human gene AHSG encoding a serum protein, alpha 2-Heremans Scmid-glycoprotein (alpha 2HSG), with heretofore unknown physiological function [15].
• Alpha 2HS-glycoprotein (AHSG) was produced by 10 of 19 hybrids; concordancy for presence or absence of protein production was 100% for human chromosome 3 [16].
• Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in a Philippine population [17].
• The availability of the AHSG cDNA clone will facilitate the analysis of its genetic control and gene expression during development and bone formation [9].
• Recombinant plasmids containing human cDNA AHSG have been isolated by screening an adult human liver library with a mixed oligonucleotide probe [9].

Anatomical context of AHSG

• Suppressive effects on neutrophil stimulation exhibited by AHSG were also specific for BCP crystals [18].
• AHSG was present in noninflammatory synovial fluids bound to synthetic HA crystals in vitro, and AHSG could be detected on native synovial fluid HA crystals [18].
• Lipolysis in adipocytes appears to be a phenotype that is particularly sensitive to variation in AHSG [3].
• The alpha(2) Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity [4].
• OBJECTIVE: Human fetuin/alpha2HS-glycoprotein (AHSG) is synthesized by hepatocytes [19].

Associations of AHSG with chemical compounds

• Of these, AHSG was the most active inhibitor of HA-induced neutrophil superoxide release, and this glycoprotein partially (60%) restored inhibitory activity to HA-adsorbed serum [18].
• AHSG is a natural inhibitor of the insulin receptor tyrosine kinase, and AHSG-null mice exhibit significantly enhanced insulin sensitivity [20].
• AHSG also bound in vitro to the related BCP crystal, octacalcium phosphate, but only minimally to calcium pyrophosphate dihydrate crystals and monosodium urate crystals [18].
• Three AHSG SNPs were associated with circulating levels of cholesterol [3].
• There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio [21].

Other interactions of AHSG

• TNF-alpha levels were negatively correlated with transferrin and AHSG levels [22].
• Similarly, in R patients, AHSG levels tended to decrease (P = 0.0942) following IFN-alpha treatment [2].
• Three members of the human cystatin gene superfamily, AHSG, HRG, and KNG, map within one megabase of genomic DNA at 3q27 [23].
• The proteins, TF, PI, and AHSG proved to be especially rich in special genetically fixed variants and polymorphisms, and F13B proved to be a powerful genetic marker to distinguish human groups [24].
• The present study examines 3 latitude-correlated polymorphisms: PGP, PGM1, and AHSG [25].

Analytical, diagnostic and therapeutic context of AHSG

• Isoelectric focusing studies in Brazilian Indians--uncovering variation of ORM, AHSG and IF [26].
• AHSG cDNA was obtained by RT-PCR from poly(A) RNA of seven liver tissue samples and subcloned into a plasmid vector [27].
• We hypothesized that functional variants of the AHSG gene segregating in the human population would reflect variation in body mass index (BMI) [5].
• Introns and the 5' and 3'-flanking regions were obtained by polymerase chain reaction (PCR) and the inverted PCR, respectively, from genomic DNA using AHSG cDNA-specific oligonucleotide primers [28].
• AHSG levels in unrelated individuals were measured by quantitative rocket immunoelectrophoresis and were 581+/-38, 542+/-31, and 494+/-23 mg/l for three major genotypes of AHSG1 homozygotes (n=99), heterozygotes (n=55), and AHSG2 homozygotes (n=22), respectively (differences were significant: P<0.001) [29].

References