The impact of the glycoprotein Ia collagen receptor subunit A(1648)G gene polymorphism on coronary artery disease and acute myocardial infarction

Platelet glycoprotein (GP) Ia is the major receptor for collagen and plays an important role in platelet adhesion and aggregation. Different gene poly morphisms have been identified that induce either various expression levels (C807T) or alterations of the tertiary structure (A(1648)G) of GPIa. Previ ously, we could demonstrate an association of the GPIa C807T dimorphism wit h nonfatal myocardial infarction. We have now analysed the influence of the GPIa A(1648)G (Br, HPA-5) dimorphism on the risk of coronary artery diseas e (CAD) and acute myocardial infarction (AMI). DNA samples from 2163 male C aucasian patients who underwent coronary angiography were genotyped by poly merase chain reaction and restriction fragment length analysis. The relatio n of the GPIa A(1648)G dimorphism to the extent of CAD was determined by mu ltiple regression analysis with adjustment for coronary risk factors. Odds ratios (OR) as an estimate of relative risk of CAD and AMI and two-tailed p -values were calculated by multiple logistic regression. In the total study sample, no association was detected between the A(1648)G dimorphism and CA D or AMI. However. upon analysis of low-risk patient subgroups we found an association of the GPIa A(1648)G polymorphism with the risk and the extent of CAD (patients with high apoAI/apoB ratio: OR 0.59. p = 0.0090: non- and ex-smokers: OR 0.66. p = 0.0131; both inclusion criteria: OR 0.44, p = 0.00 03). The relative frequency of the A(1648) allele was higher in controls wh ereas the GG(1648) genotype was overrepresented in patients with CAD. This association was also detectable when individuals with low expression levels of GPIa (C-807 homozygotes) were analysed (patients with high apoAI/apoB r atio: OR 0.44, p = 0.0045: non- and ex-smokers: OR 0.61. p = 0.0370). Our f indings indicate that the A(1648)G polymorphism of the platelet collagen re ceptor plays a role in CAD in well defined patient groups.