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Diabetologia
Published in: Diabetologia 7/2003

01-07-2003 | Article

Genetic variation of the platelet- surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with Type 2 diabetes mellitus

Authors: Dr. D. Tschoepe, B. Menart, P. Ferber, C. Altmann, M. Haude, B. Haastert, P. Roesen

Published in: Diabetologia | Issue 7/2003

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Abstract

Aims/hypothesis

The gene encoding the β3-subunit (GPIIIa) of the platelet α2β3-integrin (fibrinogen receptor) shows a polymorphism PlA1/A2 with the A2 allele putatively associated with an increased risk of acute ischaemic events. This study investigated whether Type 2 diabetes as a particular macrovascular risk factor associates with the thrombogenic PIA2 genotype.

Methods

The PlA genotype was determined in 112 consecutive Type 2 diabetic patients additionally classified according to the presence of macrovascular disease. Forty-four non-diabetic patients with angiografically documented cardiovascular disease (CAD/ AMI) and a further 59 non-diabetic subjects with no angiografical signs of CAD were investigated as genomic background control (n=103). PIA-genotyping was carried out by standard restriction fragment length analysis (RFLA) of PCR amplified lymphocyte template DNA.

Results

The overall allelic PlA2- prevalence accounted to 34.8% (39/112) in diabetic patients as compared to 14.6% (15/103) in non-diabetic patients [OR 3.1 (1.6–6.1), p<0.01].This odds ratio increased to 7.0 (2.5–19.7), (p<0.01) in subjects free of criteria of macrovascular disease. In non-diabetic control subjects without CAD there was an allelic PIA2 frequency of 10.2% (6/59) as compared to 20.5% (9/44) in patients with CAD and a history of AMI being less than either diabetes subgroup. The PIA2 prevalence in the subgroup of diabetes patients with macrovascular complications did not differ from the respective value in patients without macrovascular disease. [29.0% (20/69) vs. 44.2% (19/43)].

Conclusion/interpretation

This study confirms a trendwise association of PlA2 with severe coronary artery disease, but rather suggests an even stronger, highly significant association with the metabolic condition of Type 2 diabetes mellitus. This justifies the speculation that pathways dependent on the platelet α2β3 integrin physiology could be implicated in the pathogenesis of Type 2 diabetes which lends further support to the "common soil" hypothesis of diabetes and vascular disease.
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Metadata
Title
Genetic variation of the platelet- surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with Type 2 diabetes mellitus
Authors
Dr. D. Tschoepe
B. Menart
P. Ferber
C. Altmann
M. Haude
B. Haastert
P. Roesen
Publication date
01-07-2003
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2003
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1132-6

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