Genetic variation in MYLK and lung injury in children and adults with community-acquired pneumonia

Objective: To investigate whether selected single nucleotide polymorphisms in the myosin light chain kinase gene are associated with more severe lung injury in children and adults with community-acquired pneumonia. Previous studies have demonstrated an association between single nucleotide polymorphisms in the myosin light chain kinase gene and increased severity of acute lung injury in adults. Design: Prospective, case-control genetic association study. Setting: Three tertiary children's hospitals and one adult healthcare system. Patients: A total of 800 pediatric patients and 393 adult patients. Interventions: None. Measurements And Main Results: Genetic variation in the myosin light chain kinase gene was examined. The pediatric cohort was predominantly composed of African American (n ≤ 443) and Caucasian (n ≤ 253) children. A total of 393 patients made up the adult cohort. Within the pediatric cohort, single nucleotide polymorphisms rs16834493, rs820463, and rs9840993 were genotyped in the African American patients, whereas single nucleotide polymorphisms rs960224, rs33264, rs11718105, and rs9289225 were genotyped in the Caucasian patients. One single nucleotide polymorphism (rs820336) was genotyped in both groups. Genotyping in the adult cohort included rs820336, rs860224, rs33264, and rs11718105. Genotyping was performed using the Taqman Assay. Data were analyzed separately for African Americans and Caucasians and for children and adults. No associations were observed between the myosin light chain kinase gene single nucleotide polymorphisms genotyped in children with community-acquired pneumonia and increased severity of lung injury. Similarly, no associations were observed between myosin light chain kinase gene single nucleotide polymorphisms genotyped in adults with community-acquired pneumonia and increased severity of lung injury. Conclusions: No association between the selected single nucleotide polymorphisms in the myosin light chain kinase gene and either the need for positive-pressure ventilation or the development of acute lung injury/acute respiratory distress syndrome was observed in children with community-acquired pneumonia. This suggests that variation in this gene may play less of a role in lung injury in children or adults with community-acquired pneumonia than in adults with sepsis or trauma.