In this study, MMP-9 -1562 C/T polymorphism was associated with an increased risk of sepsis. Subgroup analyses suggested that the increased risk was more evident in the smokers, drinkers, females, and overweight individuals (BMI ≥ 25). Furthermore, the combination of smoking and CT genotype of MMP-9 -1562 C/T showed a significantly higher risk for sepsis.
MMP-9 is a pro-inflammatory biomarker belonging to a family of zinc containing endoproteases, which are implicated in chronic cell remodeling, apoptosis, adhesion and migration [19]. Since MMP-9 is mainly released by neutrophils and macrophages, this molecule is involved in the immune exacerbation in sepsis. A study conducted by Lorente et al. found that surviving patients with severe sepsis had elevated levels of MMP-9 [20]. Meanwhile, Hoffmann et al. suggested that the levels MMP-9 in patients with severe sepsis were significantly higher than that in healthy individuals [21]. Interestingly, Sachwani et al. demonstrated that there was a significant and early association between MMP-9 and blood glucose levels in in patients with severe sepsis and septic shock [19].
Recently, several studies explored the association between MMP-9 -1562 C/T polymorphism and the risk of sepsis. However, they obtained negative findings. Martin et al. firstly investigated the association between MMP-9 -1562 C/T polymorphism and sepsis risk in a Spanish population [14], and no significant association was observed. However, an association of MMP-9 levels with sepsis was also shown in their study [14]. A subsequent study from Spanish also showed that MMP-9 -1562 C/T polymorphism was not a risk factor for this Spanish population [15]. In addition, Bermúdez-Mejía et al. from Colombia showed that this SNP was not related to the risk of sepsis [16]. In addition, they found that − 1562 C/T polymorphism was not associated with MMP-9 levels and sepsis mortality [16]. Although these studies found similar results to some extent, the findings of some studies may be false-positive due to limited sample sizes. Therefore, we designed this case-control study to investigate the association between MMP-9 -1562 C/T polymorphism and sepsis risk in Chinese individuals. We found that CT or TT + CT genotype or T allele was associated with an increased risk of sepsis. To our knowledge, this is the first Chinese study to uncover an association between MMP-9 -1562 C/T polymorphism and sepsis susceptibility in Chinese Han population. Our findings were significantly different from those of other studies. Some factors may be accounted for these paradoxical results. First, clinical heterogeneity may be a potential factor. Second, the varied sample sizes may contribute to it. Third, racial difference was neglectable. Fourth, exposure factors for sepsis patients were different between these studies. Furthermore, stratified analyses showed that the risk of sepsis was significantly increased in smokers, drinkers, females, and overweight individuals (BMI ≥ 25). Therefore, the interactions between the MMP-9 -1562 C/T polymorphism and these factors may contribute to an increased risk of sepsis. To further evaluate the interactions between environmental factors (smoking or drinking) and genetic factors on sepsis susceptibility, we used the cross-over analysis and found that the combination of smoking and CT genotype of MMP-9 -1562 C/T showed a significantly higher risk for sepsis.
Potential limitations in this study should be addressed. First, the sample size of this study was not large enough, which may yield false positive results. Second, this study only investigated MMP-9 -1562 C/T polymorphism, whether other genetic variants of MMP-9 gene contributed to the genetic sepsis risk should be explored. Third, due to our use of a hospital-based case-control design, selection bias was unavoidable. Last, the potential mechanisms of MMP-9 -1562 C/T polymorphism affecting the incidence of sepsis should be investigated.
In conclusion, MMP-9 -1562 C/T polymorphism is associated with an increased risk of sepsis in Chinese Han population.