Molecular evidence for human alpha2-HS glycoprotein (AHSG) polymorphism
HUMAN GENETICS
Authors: Osawa, M; Umetsu, K; Ohki, T; Nagasawa, T; Suzuki, T; Takeichi, S
Abstract
Alpha2-HS glycoprotein (AHSG) is a human plasma glycoprotein that exhibits genetic polymorphism on isoelectric focusing (IEF). To identify the origin of two common alleles, AHSG*1 and *2, we examined nucleotide exchanges in the gene. AHSG cDNA was obtained by RT-PCR from poly(A) RNA of seven liver tissue samples and subcloned into a plasmid vector. After sequencing, we found six single nucleotide differences in comparison with the originally reported sequence. In particular, the nucleotide substitutions of C to T at amino acid position 230 and C to G at position 238 were common among the samples exhibiting phenotype 2-1 or 2. Since these substitutions might give rise to a NlaIII site and a SacI site, respectively for the potential AHSG*2, we analyzed these substitutions by PCR-RFLP using genomic DNA of 68 individuals. The result was consistent with the IEF analysis of the corresponding serum, indicating that AHSG*1 was characterized by ACG (Thr) at position 230 in exon 6 and ACC (Thr) at position 238 in exon 7, and that AHSG*2 was characterized by ATG (Met) at position 230 and AGC (Ser) at position 238.
Fetuin-A and arterial stiffness in patients with normal kidney function
REGULATORY PEPTIDES
Authors: Roos, Marcel; Richart, Tom; Kouznetsova, Tatiana; von Eynatten, Maximilian; Lutz, Jens; Heemann, Uwe; Baumann, Marcus; Staessen, Jan A.
Abstract
Aim: To evaluate the association between fetuin-A level (AHSG), its encoding gene (Thr256Ser) and arterial function in subjects with normal kidney function. Introduction: The aortic pulse wave velocity (aPWV) is a predictor for cardiovascular mortality. Fetuin-A is a calcification inhibitor and correlates negatively with increased vascular stiffness in dialysis patients. The fetuin-A polymorphism (Thr256Ser) is associated with reduced fetuin levels and accelerated vascular calcification in dialysis patients. Little is known about the role of fetuin-A as an independent predictor for the development of arterial stiffness in healthy subjects. Materials and methods: We studied 116 subjects with normal kidney function (age 47 12 years, 50 females and 66 males) of the FLEMENGHO study. Calcium measurements, plasma fetuin-A, its encoding gene (Thr256Ser) and indexes of arterial stiffness, such as aPWV and arterial distensibility, were determined. Results: Fetuin-A levels were negatively correlated with aPWV (r = -0.21, p = 0.029). After an adjustment for multiple covariables, fetuin-A levels were independently associated with aPWV (r = -030, p = 0.022) in males but not in females. Male fetuin-A SerSer carrier had lower fetuin-A levels and higher aPWV (fetuin-A: 61.9 +/- 29.0 mu g/ml; aPWV: 14.3 +/- 0.9 m/s) as compared to ThrThr (fetuin-A: 109.9 +/- 54.9 mu g/ml: aPWV: 6.4 +/- 1.3 m/s) and ThrSer carrier (fetuin-A: 100.8 +/- 52.5 mu g/ml; aPWV: 6.6 +/- 1.3 m/s). Other calcium variables were not significantly associated with arterial stiffness. Conclusion: With respect to common calcium variables, only fetuin-A level showed an inverse relation with aPWV in men with normal renal function. Male fetuin-A SerSer carriers demonstrate particularly high aortic stiffness, possibly implying a status of increased cardiovascular risk. (C) 2008 Elsevier B.V. All rights reserved.