Mean platelet volume and integrin alleles correlate with levels of integrins α(IIb)β(3) and α(2)β(1) in acute coronary syndrome patients and normal subjects.
OBJECTIVE
The interindividual variation in platelet α(2)β(1) exceeds a 2-fold variance in platelet α(IIb)β(3) level. Our objective was to parse the contribution of mean platelet volume (MPV) and integrin gene alleles to this variation in large cohorts of patients with acute coronary syndrome (ACS) and normal subjects.


RESULTS
Platelet α(IIb)β(3) and α(2)β(1) levels were measured by flow cytometry in whole blood from 320 ACS patients and 128 normal subjects and compared with MPV, platelet count, ITGA2 rs1126643, and ITGB3 rs5918 alleles. In all subjects, a strong direct correlation was found between MPV and α(IIb)β(3) level (P<0.001). Neither MPV nor α(IIb)β(3) level correlated with ITGB3 rs5918 alleles. In the case of α(2)β(1) level, MPV contributed modestly, whereas ITGA2 rs1126643 exerted a greater effect. An inverse correlation was found between MPV and the rs1126643 minor allele.


CONCLUSIONS
MPV is the major effector of platelet α(IIb)β(3) level, whereas the ITGA2 rs1126643 alleles influence α(2)β(1) level more than MPV does. The rs1126643 minor allele, associated with lower MPV, likely exerts this effect via the influence of α(2)β(1) on megakaryocyte maturation. Because of the hyperactivity of larger platelets, MPV is an accurate metric of risk for adverse outcome in ACS.
CHOC Children's Hospital, Hematology Research, 455 South Main Street, Orange, CA 92868, USA. tkunicki@choc.org
Thomas J
TJ
Kunicki
Shirley A
SA
Williams
Diane J
DJ
Nugent
Mark
M
Yeager
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001792:Blood Platelets / Q000473:pathology*; D016022:Case-Control Studies; D048429:Cell Size; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism*
D038982:Integrin alpha2beta1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex