Allelic Imbalance of mRNA Associated withα2-HS Glycoprotein (Fetuin-A) Polymorphism

Abstract

Alpha 2-HS glycoprotein (AHSG), also designated as fetuin-A, exhibits polymorphism in population genetics consisting of two major alleles of AHSG ∗ 1 and AHSG ∗ 2. The serum level in the AHSG ∗ 1 homozygote is significantly higher than that of the AHSG ∗ 2 homozygote. This study examined the molecular mechanism for the cis-regulatory expression. To quantitate allele-specific mRNA in intra-assays of the heterozygote, RT-PCR method employing primers that were incorporated to the two closely located SNPs was developed. The respective magnitudes of AHSG ∗ 1 to AHSG ∗ 2 in the liver tissues and hepatic culture cells of PLC/PRF/5 were determined quantitatively as 2.5-fold and 6.2-fold. The mRNA expressional difference of two major alleles was observed, which is consistent with that in the serum level. The culture cells carried heterozygous genotypes in rs4917 and rs4918, but homozygous one in rs2248690. It was unlikely that the imbalance was derived from the SNP located in the promotor site. Furthermore, to investigate the effect of mRNA degradation, RNA synthesis in the cell culture was inhibited potently by the addition of actinomycin-D. No marked change was apparent between the two alleles. The results indicated that the cis-regulatory expressional difference is expected to occur at the level of transcription or splicing of mRNA.

Matrix regeneration proteins in the hypoxia-triggered exosomes of shoulder tenocytes and adipose-derived mesenchymal stem cells

“…Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), a glycoprotein and protease inhibitor, stabilizes the ECM by counteracting the fibrotic changes mediated by MMPs and proinflammatory cytokines [46], [47]. Similarly, alpha 2-HS glycoprotein (AHSG) or fetuin-A, which was found to be upregulated in the exosomes of hypoxic tenocytes, exhibits multiple functions including insulin signaling, prevention of ECM calcification, immunomodulation, TGF-β signaling and acts as an endogenous ligand for TLR-4 [48], [49], [50]. Even though the role of AHSG in RCTI has not been well defined, the AHSGinhibitory effects of MMPs suggest its possible role in ECM disorganization and inflammation associated with RCTI [51].…”

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

“…Serum fetuin‐A showed significant associations with atherosclerosis, malnutrition and inflammation, and it was linked to mortality and cardiovascular events in PD patients 11 . The AHSG gene is located on chromosome 3 (3q27), and the AHSG exon polymorphism rs4918 767C/G (Thr256Ser) was closely correlated with serum fetuin‐A levels, suggesting a potential role of rs4918 in CAC and CAC progression 11–13 . Several studies showed the association of AHSG polymorphisms with vascular calcification in non‐CKD patients 14–16 .…”

“…11 The AHSG gene is located on chromosome 3 (3q27), and the AHSG exon polymorphism rs4918 767C/G (Thr256Ser) was closely correlated with serum fetuin-A levels, suggesting a potential role of rs4918 in CAC and CAC progression. [11][12][13] Several studies showed the association of AHSG polymorphisms with vascular calcification in non-CKD patients. [14][15][16] Meanwhile, the GG genotype has been shown to predict mortality in different ethnic populations of dialysis patients.…”