Other entities represented in this entry:
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11q24.2 | {Bacteremia, protection against} | 614382 | 3 | TIRAP | 606252 |
A number sign (#) is used with this entry because resistance to bacteremia, and presumably susceptibility to bacteremia, is associated with variation in the TIRAP gene (606252).
Between 1998 and 2002, Berkley et al. (2005) cultured blood on admission from 19,339 inpatients under the age of 13 years and calculated the incidence of bacteremia on the basis of the population served by a rural district hospital in Kenya. Of 1,783 infants under 60 days old, 228 (12.8%) had bacteremia, as did 866 (5.9%) of 14,787 infants 60 or more days old. Among infants under 60 days old, Escherichia coli and group B streptococci predominated among a broad range of isolates (14% and 11%, respectively). Among infants 60 or more days old, Streptococcus pneumoniae, nontyphoidal salmonella species, Haemophilus influenzae, and E. coli accounted for more than 70% of isolates. The minimal annual incidence of community-acquired bacteremia was estimated at 1,457 cases per 100,000 children among infants under 1 year old, 1,080 among children under 2 years old, and 505 among children under 5 years old. Of all in-hospital deaths, 26% were in children with community-acquired bacteremia. Of 308 deaths in children with bacteremia, 103 (33.4%) occurred on the day of admission and 217 (70.5%) occurred within 2 days. Berkley et al. (2005) concluded that community-acquired bacteremia is a major cause of death among children at a rural sub-Saharan hospital.
Resistance to bacteremia is associated with variation in the TIRAP gene (606252), which Khor et al. (2007) stated maps to chromosome 11q24.2.
TIRAP mediates downstream signaling of TLR2 (603028) and TLR4 (603030). These Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. Khor et al. (2007) reported a case-control study of 6,106 individuals from the U.K., Vietnam, and several African countries with invasive pneumococcal disease (607676), bacteremia, malaria (611162), and tuberculosis (607948). The study included 593 Kenyan children with bacteremia reported by Berkley et al. (2005). Genotyping 33 SNPs, Khor et al. (2007) found that heterozygous carriage of a leucine substitution for ser180 (S180L; 606252.0001) was associated independently with all 4 infectious diseases in the different study populations. Combining the study groups, they found substantial support for protective effect of S180L heterozygosity against these infectious diseases (p = 9.6 x 10(-8)). They found that the S180L variant attenuated TLR2 signal transduction.
Berkley, J. A., Lowe, B. S., Mwangi, I., Williams, T., Bauni, E., Mwarumba, S., Ngetsa, C., Slack, M. P. E., Njenga, S., Hart, C. A., Maitland, K., English, M., Marsh, K., Scott, J. A. G. Bacteremia among children admitted to a rural hospital in Kenya. New Eng. J. Med. 352: 39-47, 2005. [PubMed: 15635111] [Full Text: https://doi.org/10.1056/NEJMoa040275]
Khor, C. C., Chapman, S. J., Vannberg, F. O., Dunne, A., Murphy, C., Ling, E. Y., Frodsham, A. J., Walley, A. J., Kyrieleis, O., Khan, A., Aucan, C., Segal, S., and 22 others. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nature Genet. 39: 523-528, 2007. [PubMed: 17322885] [Full Text: https://doi.org/10.1038/ng1976]