Genetic Variants in Platelet Factor 4 Modulate Inflammatory and Platelet Activation Biomarkers.

Bhatnagar P, Lu X, Evans MK, Laveist TA, Zonderman AB, Carter DL, Arking DE, Fletcher CA.
Journal   Circ Cardiovasc Genet.
Species  
Analytes Measured   Fractalkine , P-Selectin
Matrix Tested   Serum
Year   2012
Volume  
Page Numbers  
Application   Cytokines and Chemokines , Angiogenesis and Vascular
Abstract
BACKGROUND: -African Americans suffer from higher prevalence and severity of atherosclerosis compared to Whites, highlighting racial and ethnic disparities in cardiovascular disease. Previous studies have pointed to the role of vascular inflammation and platelet activation in the formation of atherosclerotic lesions.

METHODS AND RESULTS: -We explored the role of genetic variation in four chemokine/chemokine receptor genes (CX3CR1, CX3CL1, CXCR3 and PF4) on systemic inflammation and platelet activation serum biomarkers (fractalkine, platelet P-selectin, PF4 and TNFα). In total, 110 SNPs were tested among 1,042 African Americans and 763 Whites. The strongest association with serum PF4 levels was observed for rs168449, which was significant in both racial groups (P-value: African Americans=0.0017, Whites=0.014, Combined=1.2x10(-4)), and remained significant after permutation-based multiple corrections (P(c)-value: Combined=0.0013). After accounting for the effect of rs168449, we identified another significant SNP (rs1435520) suggesting a second independent signal regulating serum PF4 levels (conditional P-value: African Americans=0.02, Whites=0.02). Together these SNPs explained 0.98% and 1.23% of serum PF4 variance in African Americans and Whites, respectively. Additionally, in African Americans, we found an additional PF4 variant (rs8180167), uncorrelated with rs168449 and rs1435520, associated with serum TNFα levels (P-value=0.008, P(c)-value=0.048).

CONCLUSIONS: -Our study highlight the importance of PF4 variants in the regulation of platelet activation (PF4) and systemic inflammation (TNFα) serum biomarkers.

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