dc.contributor.author | Kempaiah, P | |
dc.contributor.author | Anyona, SB | |
dc.contributor.author | Raballah, E | |
dc.contributor.author | Davenport, GC | |
dc.contributor.author | Were, T | |
dc.contributor.author | Hittner, JB | |
dc.contributor.author | Ong'echa JM, JM | |
dc.contributor.author | Perkins, DJ | |
dc.date.accessioned | 2018-01-17T08:57:19Z | |
dc.date.available | 2018-01-17T08:57:19Z | |
dc.date.issued | 2012-08 | |
dc.identifier.citation | Kempaiah, P., Anyona, S. B., Raballah, E., Davenport, G. C., Were, T., Hittner, J. B., … Perkins, D. J. (2012). Reduced interferon (IFN)-α conditioned by IFNA2 (−173) and IFNA8 (−884) haplotypes is associated with enhanced susceptibility to severe malarial anemia and longitudinal all-cause mortality. Human Genetics, 131(8), 1375–1391. http://doi.org/10.1007/s00439-012-1175-1 | en_US |
dc.identifier.uri | https://repository.maseno.ac.ke/handle/123456789/120 | |
dc.description.abstract | Severe malarial anemia (SMA) is a leading cause of pediatric morbidity and mortality in holoendemic Plasmodium falciparum transmission areas. Although dysregulation in cytokine production is an important etiology of SMA, the role of IFN-α in SMA has not been reported. As such, we investigated the relationship between IFN-α promoter polymorphisms [i.e., IFNA2 (A-173T) and IFNA8 (T-884A)], SMA, and functional changes in IFN-α production in children (n=663; <36 mos.) residing in a holoendemic P. falciparum transmission region of Kenya. Children with SMA had lower circulating IFN-α than malaria-infected children without severe anemia (P=0.025). Multivariate logistic regression analyses revealed that heterozygosity at −884 (TA) was associated with an increased risk of SMA [OR, 2.80 (95% CI, 1.22–6.43); P=0.015] and reduced IFN-α relative to wild-type (TT; P=0.038). Additional analyses demonstrated that carriage of the −173T/−884A (TA) haplotype was associated with increased susceptibility to SMA [OR, 3.98 (95% CI, 1.17–13.52); P=0.026] and lower IFN-α (P=0.031). Follow-up of these children for 36 mos. revealed that carriers of TA haplotype had greater all-cause mortality than non-carriers (P<0.001). Generation of reporter constructs showed that the IFNA8 wild-type −884TT exhibited higher levels of luciferase expression than the variant alleles (P<0.001). Analyses of malaria-associated inflammatory mediators demonstrated that carriers of TA haplotype had altered production of IL-1β, MIG, and IL-13 compared to non-carriers (P<0.050). Thus, variation at IFNA2 −173 and IFNA8 −884 conditions reduced IFN-α production, and increased susceptibility to SMA and mortality. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Pub Med Central | en_US |
dc.subject | Interferon | en_US |
dc.subject | promoter polymorphism | en_US |
dc.subject | SMA | en_US |
dc.subject | inflammatory mediators | en_US |
dc.title | Reduced interferon (IFN)-α conditioned by IFNA2 (-173) and IFNA8 (-884) haplotypes is associated with enhanced susceptibility to severe malarial anemia and longitudinal all-cause mortality | en_US |
dc.type | Article | en_US |