In this study, we aimed to investigate whether the genetic variations of PTX3, including genotype, allele and haplotype frequency, is associated with CAP occurrence in Chinese adult patients. With respect to rs2305619, rs38716527 and rs1840680, we found that SNP rsl840680 AA homozygosity was associated with CAP occurrence. The AA variant of rsl840680 was related to a lower risk of developing CAP (OR = 0.32, 95% CI = 0.11–0.91, p = 0.03).
As a key player in innate immunity and inflammation, PTX3 plays an important role in the resistance to pathogens. Previous studies on the relationship between PTX3 and pulmonary bacterial infection have been mainly concentrated on Pseudomonas aeruginosa and Streptococcus pneumoniae. P. aeruginosa is one of the most common colonizers of the lung. PTX3 has potential therapeutic effects on chronic lung infections caused by P.aeruginosa [17]. According to a previous study in a mouse model infected with P.aeruginosa, PTX3 participated in the interaction between complements and Fcγ receptors, significantly decreasing serum levels of pro-inflammatory cytokines (CXCL1, CXCL2, CCL2 and IL-1β) and reducing leukocyte recruitment of airway leukocytes [18]. GroEL in P. aeruginosa could induce PTX3 expression via NF-κB activation following signaling to Toll-like receptor 4 (TLR4), and GroEL-induced PTX3 promoted macrophage binding and phagocytosis of bacteria [19]. To notice, S. pneumoniae is the most frequent etiologic agent of community-acquired pneumonia in adults. Research findings demonstrated that S. pneumoniae infection could up-regulate the expression of PTX3 in vitro and experimental models. Hemolysin secreted by S. pneumoniae was involved in PTX3 expression and up-regulation through the JNK-MAPK signaling pathway [20].
According to previous findings, PTX3 SNPs (rs2305619, rs3816527 and rsl840680) were associated with various infectious diseases. PTX3 polymorphism is closely related to the occurrence of tuberculosis in the West African population, and haplotype GAG is considered to be a protective factor [12]. Another study focused on Caucasian patients with cystic fibrosis which demonstrated that haplotype GAG was also a protective factor for the development of P.aeruginosa colonization in the lungs [13]. In addition, He.et al. reported that rs1840680 AA genotype might be a risk factor for developing fungal pulmonary infection in COPD patients [14]. Contrary to the findings of He.et al., we found that patients with the AA genotype of rsl840680 had a lower risk of developing CAP. Because bacteria were the most common causative pathogens in CAP, we assume that the same genotype might play a different role during infection with fungi and bacteria.
Our findings suggest that the rs1840680 AA genotype might be a protective factor against the development of CAP in adults. The mechanism of PTX3 gene driven by infections in the process may involve protein expression, but the relationship between PTX3 SNPs and protein levels still remains controversial. We assume that rs1840680 AA genotype may up-regulate the expression of PTX3 when patients suffer from pulmonary bacterial infection. Some studies have found that rs1840680 AA genotype was associated with increased protein level in patients with primary liver cancer and acute myocardial infarction [21–22]. In patients with idiopathic pulmonary dysfunction after lung transplantation, PTX3 protein expression level was also increased carrying rs2305619 AA genotype [23]. However, in COPD patients with invasive pulmonary aspergillosis, compared to AG and GG genotype, rs1840680 AA genotype decreased the protein expression level [14]. These paradoxical findings may lead to pitfall of interpretation, thus further investigation in different populations is needed to confirm the role of this SNP variation.
We are aware of several limitations in our current study. Firstly, our study population reflected mild to moderate patients but not including severe pneumonia. Secondly, our study was conducted at a single medical center. Therefore, the sample size was relatively small and selection bias may have occurred. Moreover, etiological investigations were mostly negative in CAP patients from this study, so according to clinical manifestations and laboratory tests, we could only choose patients with most likely bacterial infection while exclude definite fungal diseases and active tuberculosis. In the future, we hope to gather more extensive data from multiple institutions and carry out functional studies to determine the identified SNP on the risk of CAP.