Genetic polymorphisms linked with community-acquired pneumonia
medwireNews: Seven genetic polymorphisms have been shown to be associated with community-acquired pneumonia (CAP), research shows.
For two genes, CYP1A1 and GSTM1, the association with CAP remained statistically significant after adjustment for multiple confounders.
Another gene, ABCB1, was nominally associated with CAP.
"We have provided the first experimental evidence for the associations of allelic variation at genes coding detoxification enzymes with the risk of CAP," write Lyubov Salnikova (Russian Academy of Sciences, Moscow) and colleagues in Gene.
For CYP1A1, the single nucleotide polymorphisms (SNPs) included in the analysis and associated with CAP are known to be highly functional.
CYP1A1 is a widely studied human pulmonary CYP gene-regulating enzyme. It is expressed in the epithelium of the peripheral airways and is highly inducible to pulmonary arterial hypertension (PAH).
The present study included 304 subjects with pneumonia and 455 control subjects. In 108 of the pneumonia patients, a causative agent could be identified, with Streptococcus pneumonia the most common etiologic agent.
In total, 13 polymorphic variants, including 11 SNPs, were genotyped in the pneumonia and control populations.
Seven polymorphic variants in genes CYP1A1, GSTM1, ABCB1, NOS3, IL6, CCR5, and ACE were associated with CAP.
A comparison of the distribution between the pneumonia cases and healthy controls showed the association was strongest for SNPs located within CYP1A1 (rs2606345T), CCR5 (rs333Ins), and ACE (rs4340Del).
A deletion at the GSTM1 gene was more likely to be observed in those with a previous history of CAP than in the healthy controls.
In an analysis examining the cumulative effects of multiple SNPs on CAP, individuals with CAP were three times more likely to carry between four and seven risk genotypes compared with controls. In total, 180 patients with pneumonia carried between four and seven risk genotypes compared with just 47 controls.
The ABCB1 gene encodes a membrane-bound transporter that effluxes a range of compounds from cells, while the GSTM1 enzyme has broad substrate specificity. Individuals who are GSTM1-positive can more efficiently metabolize certain drugs and are known to be "fast metabolizers."
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