Document Detail


A promoter polymorphism of the alpha2-HS glycoprotein gene is associated with its transcriptional activity.
MedLine Citation:
PMID:  17889958     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
alpha2-Heremans Schmid glycoprotein (AHSG), also designated fetuin-A, is an abundant plasma protein that is expressed in hepatocytes. AHSG/fetuin-A has diverse biological functions including regulation of calcium homeostasis and inhibition of insulin receptor tyrosine kinase activity. The aim of this study was to detect single nucleotide polymorphisms (SNPs) of the AHSG gene that can be involved in regulation of AHSG/fetuin-A expression. By a cycle sequencing method, two common SNPs in the promoter region of AHSG gene, -799A/T (rs2248690, dbSNP ID) and -425G/T (rs2077119), were identified. A reporter gene assay using HepG2 cells showed that the -799A allele had significantly higher promoter activity compared with the -799T allele. The overexpression of c-Fos/c-Jun significantly repressed transcriptional activity and a gel shift assay showed that the -799T DNA fragment had a greater affinity for transcription factor AP-1 than the -799A. In 40 unrelated healthy subjects, serum AHSG/fetuin-A levels increased with the following order of genotypes: -799TT<-799AT<-799AA (mean+/-S.E.M.; 222.1+/-11.0, 291.8+/-8.1, and 349.0+/-13.0 microg/ml, respectively, P<0.001). In conclusion, SNP rs2248690 in the promoter region of the AHSG gene affects the AHSG gene transcription, possibly by producing different association with AP-1.
Authors:
Mari Inoue; Hiroshi Takata; Yukio Ikeda; Tadashi Suehiro; Shojiro Inada; Fumiaki Osaki; Kaoru Arii; Yoshitaka Kumon; Kozo Hashimoto
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Publication Detail:
Type:  Journal Article     Date:  2007-09-24
Journal Detail:
Title:  Diabetes research and clinical practice     Volume:  79     ISSN:  1872-8227     ISO Abbreviation:  Diabetes Res. Clin. Pract.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-07     Completed Date:  2008-03-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8508335     Medline TA:  Diabetes Res Clin Pract     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  164-70     Citation Subset:  IM    
Affiliation:
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Proteins / genetics*
Carcinoma, Hepatocellular
Cell Line, Tumor
DNA Primers
Female
Gene Expression Regulation
Genes, fos
Genes, jun
Genetic Variation
Humans
Liver Neoplasms
Male
Polymorphism, Single Nucleotide*
Promoter Regions, Genetic*
Transcription Factor AP-1 / metabolism
Transcription, Genetic*
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/DNA Primers; 0/Transcription Factor AP-1; 0/alpha2HS glycoprotein

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