Correlation of Circulating MMP-9 with White Blood Cell Count in Humans: Effect of Smoking

Background: Matrix metalloproteinase-9 (MMP-9) is an emerging biomarker for several disease conditions, where white blood cell (WBC) count is also elevated. In this study, we examined the relationship between MMP-9 and WBC levels in apparently healthy smoking and non-smoking human subjects. Methods: We conducted a cross-sectional study to assess the relationship of serum MMP-9 with WBC in 383 men and 356 women. Next, we divided the male population (women do not smoke in this population) into three groups: never (n = 243), current (n = 76) and former (n = 64) smokers and compared the group differences in MMP-9 and WBC levels and their correlations within each group. Results: Circulating MMP-9 and WBC count are significantly correlated in men (R-2 = 0.13, p<0.001) and women (R-2 = 0.19, p<0.001). After stratification by smoking status, MMP-9 level was significantly higher in current smokers (mean 6 SE; 663.3 +/- 43.4 ng/ml), compared to never (529.7 +/- 20.6) and former smokers (568 +/- 39.3). WBC count was changed in a similar pattern. Meanwhile, the relationship became stronger in current smokers with increased correlation coefficient of r = 0.45 or R-2 = 0.21 (p<0.001) and steeper slope of beta = 1.16 +/- 0.30 (p<0.001) in current smokers, compared to r = 0.26 or R-2 = 0.07 (p<0.001) and beta = 0.34 +/- 0.10 (p<0.001) in never smokers. Conclusions: WBC count accounts for 13% and 19% of MMP-9 variance in men and women, respectively. In non-smoking men, WBC count accounts for 7% of MMP-9 variance, but in smoking subjects, it accounts for up to 21% of MMP-9 variance. Thus, we have discovered a previously unrecognized correlation between the circulating MMP-9 and WBC levels in humans.