Genetic Variation In Vac14 Is Associated With Bacteremia Secondary To Diverse Pathogens In African Children

Performing a genome-wide association study of Salmonella enterica serovar Typhi ( S. Typhi) invasion, Alvarez et al. (1) identify a trait-associated SNP, rs8060947, in VAC14 . is an expression quantitative trait locus for VAC14 RNA expression, and carriage of the A allele is associated with reduced VAC14 RNA and protein expression, and increased invasion of S . Typhi. VAC14-associated inhibition of S . Typhi invasion is mediated by a reduction in host cell membrane cholesterol. Carriage of the A allele at is associated with typhoid fever in Vietnamese individuals [cases = 496, controls = 500; P = 0.01, additive odds ratio (OR) = 1.38]. The authors further identify a SNP in high linkage disequilibrium with and rs8044133, located in a transcription factor binding site, which merits further investigation as the causative SNP.Alvarez et al. (1) note that cholesterol has been implicated in the invasion and pathogenesis of a wide range of pathogens (2⇓⇓–5). We therefore used previously published genome-wide association study data, describing susceptibility to bacteraemia secondary to diverse pathogens in Kenyan children (6), to explore whether genetic variation at the VAC14 locus is associated with susceptibility to invasive bacterial infections other than typhoid fever. In Kenyan children (cases = 1,536, controls = 2,677), (Fig. 1 A ) is significantly associated with all-cause bacteremia: P additive = 0.02, OR = 1.11 [95% confidence interval (CI) 1.02–1.22]. In keeping with the effect observed in typhoid, carriage of the A allele at increases risk of bacteremia.Fig. 1. rs8060947 and major causes of bacteremia … [↵][1]1To whom correspondence should be addressed. Email: james.gilchrist{at}well.ox.ac.uk. [1]: #xref-corresp-1-1