Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study.

Pneumonia is the leading cause of death amongst infectious diseases. <italic>Streptococcus pneumoniae</italic> is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene <italic>MEIS1</italic>; chromosome 2; <italic>p</italic>-value_IBS = 3.71 × 10⁻¹³) and rs576099063 (gene <italic>TSPAN15</italic>; chromosome 10; <italic>p</italic>-value_IBS = 2.36 × 10⁻⁸) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, <italic>OR9G9</italic>, <italic>MUC6</italic>, <italic>MUC3A</italic> and <italic>APOB</italic>, which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of <italic>MEIS1, TSPAN15</italic> and <italic>APOBR</italic> (encoding the receptor of the <italic>APOB</italic> protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene <italic>OR9G9</italic> has recently been related to some viral infectious diseases, while the role of mucin genes (<italic>MUC6</italic> and <italic>MUC3A</italic>), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases. [ABSTRACT FROM AUTHOR]