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dc.contributor.authorRaballah, Evans
dc.contributor.authorAnyona, Samuel B
dc.contributor.authorCheng, Qiuying
dc.contributor.authorMunde, Elly O
dc.contributor.authorHurwitz, Ivy-Foo
dc.contributor.authorOnyango, Clinton
dc.contributor.authorNdege, Caroline
dc.contributor.authorHengartner, Nicolas W
dc.contributor.authorPacheco, Maria Andreína
dc.contributor.authorEscalante, Ananias A
dc.contributor.authorLambert, Christophe G
dc.contributor.authorOuma, Collins
dc.contributor.authorObama, Henri C Jr T
dc.contributor.authorSchneider, Kristan A
dc.contributor.authorSeidenberg, Philip D
dc.contributor.authorMcMahon, Benjamin H
dc.contributor.authorPerkins, Douglas J
dc.date.accessioned2023-12-02T10:53:40Z
dc.date.available2023-12-02T10:53:40Z
dc.date.issued2021-11-19
dc.identifier.urihttps://doi.org/10.1177/15353702211056272
dc.identifier.urihttps://journals.sagepub.com/doi/abs/10.1177/15353702211056272
dc.identifier.urihttp://ir-library.mmust.ac.ke:8080/xmlui/handle/123456789/2412
dc.description.abstractSevere malarial anemia (SMA) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions. To gain enhanced understanding of predisposing factors for SMA, we explored the relationship between complement component 3 (C3) missense mutations [rs2230199 (2307C>G, Arg>Gly102) and rs11569534 (34420G>A, Gly>Asp1224)], malaria, and SMA in a cohort of children (n = 1617 children) over 36 months of follow-up. Variants were selected based on their ability to impart amino acid substitutions that can alter the structure and function of C3. The 2307C>G mutation results in a basic to a polar residue change (Arg to Gly) at position 102 (β-chain) in the macroglobulin-1 (MG1) domain, while 34420G>A elicits a polar to acidic residue change (Gly to Asp) at position 1224 (α-chain) in the thioester-containing domain. After adjusting for multiple comparisons, longitudinal analyses revealed that inheritance of the homozygous mutant (GG) at 2307 enhanced the risk of SMA (RR = 2.142, 95%CI: 1.229–3.735, P = 0.007). The haplotype containing both wild-type alleles (CG) decreased the incident risk ratio of both malaria (RR = 0.897, 95%CI: 0.828–0.972, P = 0.008) and SMA (RR = 0.617, 95%CI: 0.448–0.848, P = 0.003). Malaria incident risk ratio was also reduced in carriers of the GG (Gly102Gly1224) haplotype (RR = 0.941, 95%CI: 0.888–0.997, P = 0.040). Collectively, inheritance of the missense mutations in MG1 and thioester-containing domain influence the longitudinal risk of malaria and SMA in children exposed to intense Plasmodium falciparum transmission.en_US
dc.language.isoenen_US
dc.publisherExperimental Biology and Medicineen_US
dc.subjectComplement, component, 3 mutations ,alter, longitudinal, risk, pediatric, malaria, severe, malarial, anemiaen_US
dc.titleComplement component 3 mutations alter the longitudinal risk of pediatric malaria and severe malarial anemiaen_US
dc.typeArticleen_US


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