Haplotype analysis of the human α2‐HS glycoprotein (fetuin) gene

Abstract

Alpha2-HS glycoprotein (AHSG), which is equivalent to fetuin in other species, is a protein found in human plasma. AHSG is polymorphic with two common alleles and many variants. To examine the intragenic haplotypes and their diversity at this locus, a contiguous genomic DNA sequence (10n3 kb) was analyzed in 20 samples (40 chromosomes), and haplotypes were determined for 309 subjects. Judging from the aligned nucleotide sequences and the conserved amino acid residues comparing human and chimpanzee AHSG, it was concluded that the type 1 allele is probably older and has evolved into four major suballeles. The type 2 allele was generated from one branch of the type 1 allele. AHSG*3 and *5 variants were each found to have a single nucleotide change in exon 7, resulting in the change of an amino acid residue from Arg #** to Cys and from Asp #&) to Asn, respectively. It was noted that the AHSG*3 mutation gives rise to an additional cysteine residue, which possibly affects the conformation of the protein. The AHSG gene was found to have a low mutation rate and no apparent recombination events. Furthermore, the detected substitutions were nonhomogeneously distributed at this locus. In particular, four nonsynonymous substitutions were concentrated in the carboxyl-terminal domain. Alpha2-HS glycoprotein (AHSG) is a 46 kDa plasma protein mainly synthesized by hepatocytes. The molecule consists of two polypeptide chains produced through post-translational cleavage from a single polypeptide by enzymatic proteolysis ; the two chains are linked by a disulfide bond (Lee et al. 1987 ;Nawratil et al. 1996). AHSG is a member of the cystatin superfamily which includes kininogen and

AHSG gene variant is associated with leanness among Swedish men

“…Several segments within 1.1 kb upstream (Banine et al 2000) and within the minimal promoter (Gangneux et al 2003) that probably harbour regulatory transcription-factor-binding sites have been identified. A moderate degree of LD spanning from rs4918 to at least 1,690 bp upstream of the coding-sequence start (rs2593814) has previously been suggested from genomic sequencing of AHSG among 28 German or Japanese (Osawa et al 2001) and 24 Swedish (Dahlman et al 2004) individuals. We have found that the Thr230Met nucleotide substitution changes the existence of putative exonic splicing enhancer sites from the SF2/ASF and SRp40 sites (cognate score from 2.5 to below 0, and 2.7 to 1.3, respectively) to an SRp55 site (score from 1.16 to 3.76; Cartegni et al 2003).…”

Agaricus bisporus (Edible Mushroom Lectin) Inhibits Ocular Fibroblast Proliferation and Collagen Lattice Contraction

“…There is a possibility that the factors released during healing, particularly serum factors, might bind and neutralize ABL, although a study reported by Irazoqui et al (1992) suggests that the only serum factors which bind ABL are IgA1 and IgD. Fetuin is the major glycoprotein in calf serum (Nilsson, Norden and Svensson, 1979) but there is a similar glycoprotein in human serum which might bind to ABL (Osawa et al, 2001). A topical preparation of ABL 0 .…”

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

“…Moreover, recent work has revealed that two C/EBP-binding sites that reside within 200 bases upstream from the transcription start site are crucial for transcriptional down-regulation in inflammation (Gangneux et al 2003). The two non-synonymous substitutions in the coding region of the AHSG2 allele have been found to link at least three substitutions within 2 kb of the 5¢-flanking region of the gene (Osawa et al 2001) potentially leading to different serum levels because of the impact on transcriptional status. The causal substitutions and substantial hereditability will have to be evaluated with additional analyses that should include experimental strategies, such as promoter assays with transfected mammalian culture cells or serum measurements in a family study.…”