Association between IL-32 genotypes and outcome in infection-associated acute lung injury

INTRODUCTION Our purpose was to investigate variation within the IL-32 promoter and gene, and susceptibility to and outcomes from infection associated acute lung injury (ALI). METHODS Retrospective case-control study involving healthy individuals (controls) and patients (cases) with infection-associated ALI. Two hundred fifty-eight healthy normal controls and 251 patients with infection-associated ALI were used for comparison. The IL-32 promoter/gene was sequenced in 52 healthy Caucasian individuals to identify single nucleotide polymorphisms (SNPs). Allelic discrimination was performed on 11 SNPs to determine differences between cases and controls and outcomes in patients with infection associated ALI. RESULTS Logistic and normal regression models were used to evaluate the associations with SNPs in cases and controls, and outcomes in patients with infection associated ALI. rs12934561, an intronic SNP, was found to be associated with risk for ALI in the case-control study and with more severe clinical course, as shown by increased time on the ventilator and the presence of fluid unresponsive hypotension. Further, it was found that rs12934561 has gender-specific effects and strongly interacts with other SNPs. CONCLUSIONS A common IL-32 genotype, rs12934561, is associated with the risk of ALI as well as the need for prolonged mechanical ventilatory support. This finding suggests that IL-32 is not only involved in the initiating inflammatory and cellular events that result in ALI, but also participates in determining the severity of pulmonary dysfunction associated with ALI.