alpha2-Heremans-Schmid Glycoprotein Gene Research Articles

The SNP (g.198655287 G>A) of AHSG gene polymorphism and its association with mineral composition in Indonesia lamb meat

The AHSG (Alpha2-Heremans-Schmid Glycoprotein) gene is indicated to have an essential role in mineral composition. This study aimed to identify the polymorphism of the AHSG gene and its association with the mineral composition of Indonesian lamb meat. The samples were 85 rams Indonesian sheep, consisting of 70 Javanese thin-tailed sheep (JTTS) and 15 Jonggol sheep (JS). AHSG gene polymorphism was analyzed using the PCR-RFLP technique with the EagI restriction enzyme. The AHSG gene association was analyzed using the T-test. The Hardy-Weinberg equilibrium analysis showed that the AHSG was polymorphic with three genotypes, i.e., GG, GA, and AA. The AHSG gene with mineral composition was associated with significance (P<0.05) on the content of Fe (iron), Zn (Zinc), and Se (Selenium). The AA genotype is the recommended genotype due to its high mineral composition. The AHSG gene (SNP g.198655287 G>A) can be used as a genetic marker for the molecular-based selection of lamb with high mineral composition.

Alpha 2-Heremans-Schmid glycoprotein gene polymorphism (rs4918) is associated with coronary artery calcification in incident peritoneal dialysis patients.

Coronary artery calcification (CAC) is a common and severe complication in peritoneal dialysis (PD) patients, and it progresses in a majority of patients. Fetuin-A, encoded by the alpha 2-Heremans-Schmid glycoprotein (AHSG) gene, is a serum calcification inhibitor. The study aimed to examine the role of AHSG gene polymorphism rs4918 in CAC and CAC progression of PD patients. Incident PD patients at Huashan Hospital Fudan University in China from August 2007 to July 2018 were recruited in this prospective study and followed up for 2 years. Patients underwent CAC measurements at recruitment and 2 years later. AHSG gene polymorphism rs4918 and serum fetuin-A were determined at baseline. The demographic characteristics, clinical data, and laboratory data were collected during the follow-up period. Binary logistic regression was performed to explore the association between rs4918 with CAC and CAC progression. A total of 202 PD patients (112 men, 55.4%) were recruited, with a mean age of 54 ± 16 years. The multivariate logistic regression identified genotype GG as an independent risk factor that correlates to CAC (odds ratio [OR]=2.153; 95% CI: 1.182-3.925; p=.012) and CAC progression (OR=2.482; 95% CI: 1.422-4.330; p=.001). The serum fetuin-A level was influenced by the rs4918 variants of AHSG, with a dose-dependent effect depending on the number of the G allele. AHSG gene polymorphism rs4918 affects serum fetuin-A levels and is significantly associated with both CAC and CAC progression in a cohort of patients receiving PD.

Is there an association between alpha 2-Heremans-Schmid glycoprotein (AHSG) gene Thr256Ser polymorphisms with aortic calcification in regular hemodialysis patients in Medan, Indonesia.

Aim Alpha2-Heremans-Schmid glycoprotein (AHSG), a circulating plasma protein, plays an essential role in bone and vascular mineralization. The impact of AHSG gene polymorphisms on aortic calcification in haemodialysis patients was inconsistent. We performed this study to clarify precise association among AHSG gene Thr256Ser single-nucleotide polymorphisms and aortic calcification. Methods Patients on stable regular haemodialysis treatment for more than thirty months were included in a cross-sectional study at Rasyida Renal Hospital Medan. Lateral spine X-rays were performed to evaluate the aortic calcification. Genotyping for the polymorphisms was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. Results Aortic calcification was detected in 69.8% of patients. From 106 patients, 49 patients (46.2 %) had CC (Thr/Thr), 54 (51.0%) had CG (Thr/Ser) and three (2.8%) patients had GG (Ser/ Ser) polymorphism. The proportion of patients with heterozygous or homozygous G allele (CG and GG genotypes) is more likely (91.2%) to have aortic calcification. The bivariate analysis showed that Thr256Ser polymorphism (G allele) was associated with increased risk for aortic calcification (PR=2.03; 95% CI 1.48-2.80; p<0.001). However, overall results from multivariate analysis showed that Fetuin-A level <204 pg/mL (PR=22.0; 95% CI 3.32-145.91; p=0.001) and IL-6 level ≥53.05 mg/dL (PR=19.50; 95% CI 2.87-132.41; p=0.002) were the major risk factors for the occurrence of aortic calcification. Conclusion AHSG Thr256Ser gene polymorphism showed an association with aortic calcification in regular haemodialysis patients, but Fetuin-A and IL-6 have a dominant role in the development of aortic calcification.

Minor variant of AHSG gene 767C>G polymorphism may decrease the risk of gestational diabetes mellitus

Insulin resistance plays a central role in the development of gestational diabetes mellitus (GDM). The fetuin A molecule, of which serum level increases during pregnancy, is an inhibitor of insulin receptor tyrosine kinase and it is associated with insulin resistance. The aim of this study is to research the relationship of –843A>T (rs2248690) and 767C>G (rs4918) polymorphisms in the alpha-2-Heremans Schmid glycoprotein (AHSG) gene which is responsible for the synthesis of fetuin A and its association with (GDM). In this study, 83 pregnant women with GDM who applied to the Obstetrics and Gynaecology Clinics and 100 normal pregnants enrolled as the control group. Genotyping of AHSG gene polymorphisms was performed by using the TaqMan allelic discrimination kit with real time PCR device. In our study, homozygous GG genotype which was polymorphic in the 767C>G polymorphism of AHSG gene was found significantly low in the patient group (p < .05). Genotype distribution of AHSG gene –843A>T polymorphism was not statistically significant between the patient and control groups (p > .05). Our results showed that homozygous GG variant of AHSG gene 767C>G polymorphism may have protective effect against the development of GDM.Impact statementWhat is already known on this subject? Insulin resistance has a central role in the development of gestational diabetes mellitus (GDM). The fetuin A molecule is an inhibitor of insulin receptor tyrosine kinase and it is associated with insulin resistance. The –843T>A and 767G>C polymorphisms of AHSG gene encoding fetuin A are affects serum fetuin A level. In a single study investigating the relationship between GDM and AHSG gene 767G>C polymorphism, there was no significant difference in genotype distribution but it was reported that the frequency of G allele increased in GDM group and this increase provided a weak risk or predisposition.What the results of this study add? The present study revealed that homozygous GG variant of AHSG gene 767C>G polymorphism may decrease the risk of GDM.What the implications are of these findings for clinical practice and/or further research? Protective effect of homozygous GG variant of AHSG gene 767C>G polymorphism, can be used as a molecular biomarker to predict the development of GDM. These results should be supported by further research in larger sample sizes.

Identification of Single Nucleotide Polymorphism and Association Analysis of Alpha 2-Heremans Schmid Glycoprotein (AHSG) Gene Related to Fatty Acid Traits in Sheep

Fatty acid (FA) composition of meat is regulated by many genes. The aim of this study was to identify Single Nucleotide Polymorphism (SNP) of Alpha 2-Heremans Schmid Glycoprotein (AHSG) gene and analyze its association with fatty acid (FA) traits in lambs. The study used a total of 67 rams of 12 months with average body size of 25-30 kg, consisted of 20 heads of Javanese Fat-Tailed (JFT) sheep, 17 heads of Javanese Thin-Tailed (JTT) sheep, 10 heads of Composite Garut (CG) sheep, 10 heads of Compass Agrinak (CA) sheep and 10 heads of Barbados Black Belly Cross (BC) sheep. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) were used to identify the single nucleotide polymorphisms (SNP) of AHSG gene. Association of AHSG genotypes with fatty acid traits was performed using General Linear Model by SAS 9.4 program. The SNP of AHSG gene was polymorphic with three genotypes (GG, GA and AA). In combined population, the genotype frequency of GG, GA and AA were 0.25, 0.13 and 0.62, respectively. The Chi-square test revealed that the locus of AHSG (g. 198655287 (G&gt;A) was in Hardy-Weinberg equilibrium, except in Composite Garut (CG), Compass Agrinak (CA) and Barbados Black Belly Cross (BC) sheep breeds. The g.198655287 (G&gt;A) SNP of AHSG gene was significantly associated (P&lt;0.05) with saturated fatty acid, including &lt;a href="https://en.wikipedia.org/wiki/Capric_acid"&gt;capric acid (C10:0)&lt;/a&gt;, palmitic acid (C16:0), heptadecanoic acid (17:0), &lt;a href="https://en.wikipedia.org/wiki/Arachidic_acid"&gt;arachidic acid (C20:0)&lt;/a&gt;, heneicosylic acid (C21:0), &lt;a href="https://en.wikipedia.org/wiki/Behenic_acid"&gt;behenic acid (C22:0)&lt;/a&gt;, &lt;a href="https://en.wikipedia.org/wiki/Tricosylic_acid"&gt;tricosylic acid (C23:0)&lt;/a&gt;, &lt;a href="https://en.wikipedia.org/wiki/Lignoceric_acid"&gt;lignoceric acid (C24:0)&lt;/a&gt;; with monounsaturated fatty acids, including &lt;a href="https://en.wikipedia.org/wiki/Palmitoleic_acid"&gt;palmitoleic acid (C16:1)&lt;/a&gt;; oleic acid (C18:1n9c); eicosenoic acid (C20:1); nervonic acid (C24:1) and with polyunsaturated fatty acids, including linoleic acid (C18:2n6c); γ-Linolenic acid; α-Linolenic acid; &lt;a href="https://en.wikipedia.org/w/index.php?title=Eicosadienoic_acid&amp;action=edit&amp;redlink=1"&gt;eicosadienoic acid (C20:2)&lt;/a&gt;; dihomo-gamma-linolenic acid; arachidonic acid; &lt;a href="https://en.wikipedia.org/w/index.php?title=Docosadienoic_acid&amp;action=edit&amp;redlink=1"&gt;docosadienoic acid(C22:2)&lt;/a&gt;; eicosapentanoic and docosahexaenoic acid. The SNP g. 198655287 (G&gt;A) of AHSG gene may be a useful marker for selecting and producing sheep meat having desirable fatty acids.

Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis

Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. The prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was highly related to serum fetuin-A levels (P < 0.001). Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and 0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators.

Association of alpha 2-Heremans-Schmid glycoprotein gene polymorphisms with its serum levels

To identify the single nucleotide polymorphisms (SNPs) of the alpha2-Heremans-Schmid glycoprotein (AHSG) gene and assess their association with the AHSG serum level. The SNPs of the AHSG gene were identified from 30 unrelated Han individuals from Guangzhou area by resequencing. Linkage disequilibrium(LD) was performed to observe the linkage disequilibrium pattern. Then tagSNPs were genotyped in 192 Han individuals from Beijing and 424 Han individuals from Guangzhou area. Finally, luciferase reporter gene assay was performed to determine whether the SNPs affected the promoter activity. Serum AHSG concentrations were measured in the 192 subjects from Beijing using ELISA. Eight SNPs were detected in total. The linkage disequilibrium profile in the Guangzhou Han population was different from that in the Beijing Han population. However, the allele and genotype frequencies of tagSNPs between the two Han populations were not significantly different. The reporter gene assay showed that the -799A allele had significantly higher promoter activity than the -799T allele. Multiple regression analysis revealed that only the rs2248690 SNP was an independent contributor to serum AHAG concentration. The rs2248690 SNP in the promoter region of the AHSG gene might affect the AHSG gene transcription.

High Glucose Induces Transactivation of the .ALPHA.2-HS Glycoprotein Gene Through the ERK1/2 Signaling Pathway

Alpha2-Heremans Schmid glycoprotein (AHSG), also known as fetuin-A, is secreted from the liver and inhibits tyrosine kinase activity of the insulin receptor. Hyperglycemia in type 2 diabetes is not only a secondary manifestation of insulin resistance, but could also be responsible for directly inducing insulin resistance in target tissues. In this study, we examined the effect of high glucose (HG) on AHSG gene transcription in the human hepatoma cell line HepG2. AHSG transcriptional activity and protein expression were evaluated using reporter gene assays and Western blot analysis, respectively. D-glucose, but not L-glucose or mannitol, dose-dependently enhanced AHSG promoter activity. HG (25 mM) also increased AHSG protein expression. No protein kinase C inhibitors (bisindolylmaleimide, Ro-31-8220), an inhibitor of hexosamine biosynthesis pathway (6-diazo-5-oxo-L-norleucine), or a superoxide radical scavenger (tempol) affected HG-induced transactivation. MAPK/ERK kinase inhibitors (PD98059, U0126), but not the JNK inhibitor (SP600125) or p38 inhibitor (SB203580), significantly inhibited promoter activation by HG. Our data suggest that HG enhances AHSG transcription through activation of the ERK1/2 signaling pathway. Increased AHSG expression in the liver may be a cause of glucose toxicity in the diabetic state.

Polymorphism of the AHSG gene is associated with increased adipocyte β2-adrenoceptor function

The alpha(2) Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity. The Met/Met genotype of the common single-nucleotide polymorphism (SNP), rs4917, in the AHSG gene has been shown to be associated with reduced plasma levels as well as lower body fat. Here, we studied the association of this variation with subcutaneous adipocyte lipolysis. Ninety-three obese and nonobese healthy men were genotyped for Thr230Met, and subcutaneous adipose tissue biopsies were analyzed for lipolysis characteristics. The Met/Met genotype was associated with a marked increase of 1.5 log units in the lipolytic sensitivity to the beta2-adrenoceptor agonist terbutaline (P=0.0008) as compared with the Thr/Thr and Thr/Met genotypes. This corresponds to an approximately 35-fold increase in beta2-adrenoceptor function. The genotype effect was independent of body mass index and waist circumference. In contrast, lipolytic sensitivity to both the beta1-adrenoceptor agonist dobutamine (P=0.25) and the alpha2A-adrenoceptor agonist clonidine (P=0.54) was unaffected by the Thr230Met variation. Moreover, no difference in either maximal stimulation or inhibition of lipolysis was found between genotypes. 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.

Genetic association of alpha2-Heremans–Schmid glycoprotein polymorphism with late-onset Alzheimer's disease in Italians

Alpha2-Heremans–Schmid glycoprotein (AHSG), also known as fetuin-A, is a highly glycosylated protein which has been recently reported to be decreased in the cerebrospinal fluid of patients with Alzheimer's disease. AHSG is genetically polymorphic and two common alleles, AHSG*1 and AHSG*2, have been described. 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. In patients with LOAD, the genotype distribution was 184 AHSG 1*1, 44 AHSG 1*2, 7 AHSG 2*2, and was significantly different from that observed in the 235 control subjects (117 AHSG 1*1, 103 AHSG 1*2, 15 AHSG 2*2) ( χ 2 = 41.50, P < 0.0001). After allowance for age, gender and APOE ɛ4 status, multivariate logistic regression analysis revealed that the adjusted odds ratio for the development of LOAD in AHSG 1*1 homozygotes was 3.90 (95% CI: 2.58–5.90, P < 0.0001). These results suggest that the AHSG gene polymorphism may be associated with LOAD in Italians. Additional studies are warranted to examine the biological relevance of AHSG in the pathophysiology of neurodegenerative disorders.

AHSG gene variant is associated with leanness among Swedish men

Alpha(2) Heremans-Schmid glycoprotein (AHSG) is a plasma protein inhibiting the activity of the insulin receptor tyrosine kinase. Ahsg knock-out mice have increased insulin sensitivity and are resistant to diet-induced obesity. We hypothesized that functional variants of the AHSG gene segregating in the human population would reflect variation in body mass index (BMI). 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. The G/G genotype for rs2593813 was more common among lean than among obese and overweight individuals (odds ratio = 2.01, P = 0.009), whereas rs2593813 was in strong linkage disequilibrium (|D'| > or = 0.97) with rs4917 and rs4918. Homozygosity for the rs2593813:G-rs4917:Met-rs4918:Ser haplotype conferred an increased risk for leanness (odds ratio=1.90, P = 0.027). rs4917:Met and rs4918:Ser have previously been associated with lower AHSG protein level. A common variant of AHSG, previously associated with a lower AHSG protein level, is thus more common among lean than obese and overweight men, supporting the results from Ahsg knock-out mice, namely, that AHSG modulates body mass.