Common Genetic Variant Increases Risk of Bacterial Pneumonia

Known risk factors include advanced age, smoking, and underlying medical conditions. Genetic variation may also influence susceptibility by altering innate immune defenses in the airways. New findings demonstrate that a common genetic variant can weaken lung defenses against bacteria.

Researchers at Lund University, working with Skåne University Hospital, identified a common genetic variant that affects the immune receptor Dectin-1. The variant, identified in the publication as CLECh7A Y238*, is carried by roughly one in seven Europeans. Dectin-1 is found on cells in lung tissue, where it recognizes foreign substances and helps activate immune responses against infection.

The analysis included just over 28,000 participants in the Malmö Diet and Cancer Study who were followed for an average of more than 17 years. During this period, approximately 5,500 cases of pneumonia were recorded. The research also included mechanistic experiments in mice, with the overall study incorporating clinical, epidemiological, registry-based, retrospective, longitudinal, case-control, animal, in vitro, and in vivo components.

Carriers of the genetic variant had an approximately 12% higher risk of developing pneumonia, even after accounting for smoking, body weight, and medical conditions affecting the immune system. The increased risk remained when the analysis was restricted to bacterial pneumonia. In mice, absence or reduced function of Dectin-1 impaired clearance of pneumococci and Haemophilus, two common bacteria that can cause respiratory tract infections, providing further evidence of the receptor’s role in lung defenses.

The findings were published in eBioMedicine, The Lancet Discovery Science, in a study titled “The CLECh7A Y238* variant and susceptibility to pneumonia: a prospective population-based cohort study and mechanistic investigation.” The research indicates a previously unknown mechanism by which the lungs’ immune system detects bacteria. The findings may contribute to understanding why some people are more susceptible to infections than others.

“In my 30 years as a researcher, this is one of the studies I am most proud of. I began researching Haemophilus as far back as 1999, and my long experience of the bacterium has been crucial to this work. But it is only with today’s techniques, including whole-genome sequencing, that we have been able to analyse the participants’ genetic background and achieve these results,” said Kristian Riesbeck, professor of clinical bacteriology at Lund University and senior consultant in clinical microbiology at Skåne University Hospital.

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