Genetic variation of the platelet- surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with Type 2 diabetes mellitus.
OBJECTIVE
The gene encoding the beta(3)-subunit (GPIIIa) of the platelet alpha(2)beta(3)-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)].


CONCLUSIONS
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 alpha(2)beta(3) 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.
Tschoepe
D
D
German Diabetes Clinic, German Diabetes Research Institute, Heinrich Heine University of Duesseldorf, Auf'm Hennekamp 65, 40225 Duesseldorf, Germany. dtschoepe@hdz.nrw.de
Menart
B
B
Ferber
P
P
Altmann
C
C
Haude
M
M
Haastert
B
B
Roesen
P
P
D019943:Amino Acid Substitution; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D012307:Risk Factors
D006442:Glycated Hemoglobin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex