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LincRNA Linked to Risk of Pneumococcal Bloodstream Infection in Kenyan Children

NEW YORK (GenomeWeb) – A long intergenic non-coding RNA, or lincRNA, gene identified in children from Kenya appears to contribute to susceptibility to bacterial bloodstream infections in this population, according to a study in the American Journal of Human Genetics.

Members of the Wellcome Trust Case Consortium 2's Kenyan Bacteremia Study Group did a genome-wide association study involving more than 4,500 children in Kilifi, a town on the eastern coast of Kenya. When they compared genetic patterns in infants with or without bloodstream infections caused by Streptococcus pneumoniae bacteria, a lincRNA gene on chromosome 7 stood out: AC011288.2.

The team's analysis of 1000 Genomes Project data indicated that the bacteremia-associated AC011288.2 allele was derived and specific to African populations. It turned up with a frequency of less than 3 percent in bacteremia-free children, but was found in more than 6 percent of children who suffered from S. pneumoniae-related bloodstream infections.

"The genetic variants we identified are found only in African populations" and carry a doubled risk of developing bacteremia when infected with the Streptococcus pneumoniae bacteria, co-first author Anna Rautanen, with the University of Oxford's Wellcome Trust Centre for Human Genetics, said in a statement.

"This discovery therefore provides clues in the pressing search for new ways to target the disease," Rautanen added.

The researchers started by using the ImmunoChip array to genotype 429 Kenyan children younger than 13 years old with bacteremia and 2,677 without. When they compared almost 10 million directly genotyped or imputed SNPs in the cases and controls, a set of 17 suspicious SNPs on chromosome 7 stood out in the pneumococcal bacteria-related bloodstream infection cases.

This chromosome 7 locus — which was also associated with bacteremia in the team's replication analysis of for another 113 cases and 1,336 controls from the Kenyan population — contained two lincRNA genes.

The team focused on AC011288.2, which is expressed in placenta and white blood cell tissues. In contrast, the other lincRNA at the bacteremia-associated locus was not detected in prior expression studies of two-dozen human tissue or cell types.

In their follow-up experiments, the researchers saw AC011288.2 expression specifically within the neutrophils — a group of white blood cells that's believed to help the immune system oust pneumococcal bacteria.

When they tapped the GWAS data to search for variants linked to bloodstream infections caused by all types of bacteria, the investigators identified a genome-wide significant association at a variant in the HBB gene that is already recognized as a contributor to sickle hemoglobin production.

"At both loci, the disease-associated alleles are rare in individuals without African ancestry," Rautanen and co-authors noted, "and exert a large effect on the likelihood of developing bacteremia."

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