A promoter polymorphism of the alpha 2-HS glycoprotein gene is associated with its transcriptional activity
DIABETES RESEARCH AND CLINICAL PRACTICE
Authors: Inoue, Mari; Takata, Hiroshi; Ikeda, Yukio; Suehiro, Tadashi; Inada, Shojiro; Osaki, Fumiaki; Arii, Kaoru; Kumon, Yoshitaka; Hashimoto, Kozo
Abstract
alpha 2-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, -799 A/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 mu g/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. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
Preeclampsia is associated with decreased serum alpha(2)-HS glycoprotein (fetuin-A) concentration
HYPERTENSION RESEARCH
Authors: Molvarec, Attila; Kalabay, Laszlo; Derzsy, Zoltan; Szarka, Andras; Halmos, Amrita; Stenczer, Balazs; Arnaud, Philippe; Karadi, Istvan; Prohaszka, Zoltan; Rigo, Janos, Jr.
Abstract
The purpose of this study was to determine serum alpha 2-HS glycoprotein (AHSG) concentration and its diagnostic accuracy in preeclampsia. In this case-control study, the serum C-reactive protein (CRP) and AHSG levels were measured in 93 preeclamptic patients and in 127 healthy pregnant women by immunoturbidimetry and radial immunodiffusion. The serum CRP levels were significantly higher, whereas the serum AHSG concentrations were significantly lower in the preeclamptic group than in the control group (median (25th to 75th percentile), CRP: 6.71 mgl(-1) (2.76-12.69) vs. 3.38 mgl(-1) (1.69-7.27), respectively; AHSG: 660 mu g ml(-1) (612-768) vs. 744 mu g ml(-1) (660-816), respectively; P<0.001 for both). In preeclamptic patients, the serum AHSG concentrations showed significant inverse correlations with systolic blood pressure and serum CRP levels. A low serum AHSG level (<= 720 mu g ml(-1)) was significantly associated with preeclampsia (adjusted odds ratio (95% confidence interval): 3.69 (1.82-7.51); P<0.001). According to the receiver operating characteristic curves, the measurement of serum AHSG concentrations was as accurate as that of serum CRP levels to detect preeclampsia. In conclusion, serum AHSG concentration is decreased and reflects-at least partly-systemic inflammation in preeclampsia. Hypertension Research (2009) 32, 665-669; doi:10.1038/hr.2009.79; published online 29 May 2009