Full Length ArticleThe SH2B3 and KCNK5 loci may be implicated in regulation of platelet count, volume, and maturity

- In stable CAD patients, two genetic markers of CAD and MI were associated with indices of platelet size.
- Our results suggest a role for the KCNK5 locus in the regulation of platelet size and maturity.
- We confirm an association between the SH2B3 locus and platelet count.

IntroductionIn recent genome-wide association studies, coronary artery disease (CAD) and myocardial infarction (MI) have been linked to a number of genetic variants, but their role in thrombopoiesis is largely unknown.AimWe investigated the association between CAD and MI-associated genetic variants and five thrombopoiesis-related indices: platelet count (PC), mean platelet volume (MPV), immature platelet count (IPC), immature platelet fraction (IPF), and serum thrombopoietin (TPO).MethodsWe genotyped 45 genome-wide significant CAD/MI-markers in 879 stable CAD patients. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. Platelet indices were analysed using the Sysmex XE-2100 haematology analyser. TPO was measured by ELISA.ResultsTwo variants were nominally associated with several indices; for rs10947789 (KCNK5), the adjusted geometric mean was 2% higher for MPV (95% confidence interval: 1-2%, p = 0.002), 6% for IPC (0-12%, p = 0.033), and 9% for IPF (3-16%, p = 0.004) per CAD risk allele. Moreover, an 11% lower TPO (3-19%, p = 0.010) was observed. Rs3184504 (SH2B3) was associated with a higher adjusted geometric mean of 3% (1-6%, p = 0.003) per CAD risk allele for PC, and an 11% (5-17%, p < 0.001) lower TPO. Furthermore, the adjusted IPC was 5% (0-9%, p = 0.037) lower per CAD risk allele for PC, whereas IPF levels did not vary across genotypes.ConclusionAs a novel finding, our study suggests a role for KCNK5 in the regulation of platelet size and maturity. Furthermore, our findings confirm an association between the SH2B3-locus and platelet count.