rs1840680 single nucleotide polymorphism in Pentraxin 3: a potential protective biomarker of severe community-acquired pneumonia.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) of pentraxin 3 (PTX3) are associated with various outcomes of lung infections. This study aimed to analyze the relationship between PTX3 polymorphisms and the severity of community-acquired pneumonia (CAP). METHODS: This is a retrospective case-control study comprising 43 patients with severe CAP (SCAP) and 97 patients with non-severe CAP. Three SNPs in the PTX3 gene (rs2305619, rs3816527, and rs1840680) from peripheral blood samples were genotyped by real-time polymerase chain reaction. The association between each SNP and the CAP severity was analyzed by logistic regression analysis. RESULTS: We found that the rs1840680 polymorphism was significantly associated with CAP clinical severity. However, no such association was observed for the genotypes and allele frequencies of rs2305619 or rs3816527. The PTX3 rs1840680 AG genotype was an independent factor for a lower risk of SCAP after multivariate logistic regression analysis. Male sex and coronary heart disease were associated with an increased risk of SCAP. CONCLUSIONS: The PTX3 rs1840680 AG genotype was found to be associated with a lower risk of SCAP, and may serve as a potential protective biomarker to help clinical judgment and management.

Pentraxin-3 polymorphisms and pulmonary fungal disease in non-neutropenic patients.

BACKGROUND: Pentraxin 3 (PTX3) plays a non-redundant role in innate immunity against fungal diseases. Although single nucleotide polymorphisms (SNPs) of PTX3 are associated with a higher risk of invasive aspergillosis among the immunosuppressed population and chronic obstructive pulmonary disease patients, it is unknown whether PTX3 genetic variants influence the risk of pulmonary fungal disease in immunocompetent patients. METHODS: To investigate the association between PTX3 gene polymorphisms and pulmonary mycosis in non-neutropenic patients, we conducted a case-control study in a tertiary hospital department. Forty-five patients were identified using the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) and enrolled in the case group. Of these patients, 15 had allergic bronchopulmonary aspergillosis (ABPA), 10 had invasive pulmonary aspergillosis (IPA), 18 had pulmonary cryptococcosis, and 2 had other types of pulmonary mycosis. One hundred and twenty-two non-neutropenic inpatients not infected by fungal disease were randomly selected as the control group. We detected three SNPs (rs2305619, rs3816527, and rs1840680) within the PTX3 gene using polymerase chain reaction sequencing and compared their associations with different types of pulmonary fungal disease. RESULTS: Three SNPs were consistent with Hardy-Weinberg equilibrium (HWE). SNP rs2305619 was in linkage disequilibrium with rs3816527 (D'=0.85) and rs1840680 (D'=0.85), respectively. There was no difference in the genotypic distribution and haplotype frequency of the SNPs between the case group and the control group. When we focused on invasive mold infections as a subgroup, we found that the SNP rs3816527 CC homozygote was associated with a higher risk of IPA (OR, 7.37; 95% CI, 0.93-44.44; P=0.033), while the rs3816527 AA homozygote might lower the risk of pulmonary cryptococcosis (OR, 0.35; 95% CI, 0.11-0.96; P=0.047). No genotypic distribution differences were observed for the other two SNPs (rs2305619 and rs1840680). When it came to the comparison between ABPA subgroup and control group, no difference in single nucleotide polymorphism was observed. CONCLUSIONS: This study showed that the SNP rs3816527 is associated with IPA in non-neutropenic patients. Further investigations in large populations are needed to validate this genetic predisposition. Functional studies are also required.