Reduced interferon (IFN) –α conditioned by IFNA2 (-173) and IFNA8 (-884) haplotypes is associated with enhanced susceptibility to severe malarial anaemia and longitudinal all-cause mortality
| dc.contributor.author | Were, T. | |
| dc.contributor.author | Kempaiah, P. | |
| dc.contributor.author | Anyona, S. B. | |
| dc.contributor.author | Raballah, E. | |
| dc.contributor.author | Davenport, G. C. | |
| dc.contributor.author | Hittner, James B. | |
| dc.contributor.author | Ong'echa, J. M. | |
| dc.contributor.author | Perkins, D. J. | |
| dc.date.accessioned | 2013-12-17T12:40:17Z | |
| dc.date.available | 2013-12-17T12:40:17Z | |
| dc.date.issued | 2012-08 | |
| dc.description | doi: 10.1007/s00439-012-1175-1 | en_US |
| 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 months) 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 months 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.identifier.citation | PubMed, 131(8):1375-91, August 2012 | en_US |
| dc.identifier.uri | http://ir-library.ku.ac.ke/handle/123456789/8091 | |
| dc.language.iso | en | en_US |
| dc.publisher | PubMed | en_US |
| dc.title | Reduced interferon (IFN) –α conditioned by IFNA2 (-173) and IFNA8 (-884) haplotypes is associated with enhanced susceptibility to severe malarial anaemia and longitudinal all-cause mortality | en_US |
| dc.type | Article | en_US |