Tumour necrosis factor alpha promoter polymorphism, TNF-238 is associated with severe clinical outcome of falciparum malaria in Ibadan southwest Nigeria

Abstract

Tumour necrosis factor (TNF) - α has been shown to play an important role in the pathogenesis of falciparum malaria. Two TNF promoter polymorphisms, TNF-308 and TNF-238 have been associated with differential activity and production of TNF. In order to investigate the association between TNF-308 and TNF-238 and the clinical outcome of malaria in a Nigerian population, the two TNF polymorphisms were analysed using Sequenom iPLEX Platform. A total of 782 children; 283 children with uncomplicated malaria, 255 children with severe malaria and 244 children with asymptomatic infection (controls) were studied. The distribution of TNF-308 and TNF-238 genotypes were consistent with the Hardy-Weinberg equilibrium. Distribution of both TNF polymorphisms differed significantly across all clinical groups (TNF-308: p=0.007; TNF-238: p=0.001). Further tests for association with severe malaria using genotype models controlling for age, parasitaemia and HbAS showed a significant association of the TNF-238 polymorphism with susceptibility to severe malaria (95% CI=1.43-6.02, OR=2.94, p=0.003237) The GG genotype of TNF-238 significantly increased the risk of developing cerebral malaria from asymptomatic malaria and uncomplicated malaria (95% CI=1.99-18.17, OR=6.02, p<0.001 and 95% CI=1.78-8.23, OR=3.84, p<0.001 respectively). No significant association was found between TNF-308 and malaria outcome. These results show thegenetic association of TNF-238 in the clinical outcome of malaria in Ibadan, southwest Nigeria. These findings add support to the role of TNF in the outcome of malaria infection. Further large scale studies across multiple malaria endemic populations will be required to determine the specific roles of TNF-308 and TNF-238 in the outcome of falciparum malaria infection.

The Glycosylphosphatidylinositol Transamidase Complex Subunit PbGPI16 of Plasmodium berghei Is Important for Inducing Experimental Cerebral Malaria

“…GPIs and GPI anchors are thought to be among the major inducers of the proinflammatory cytokine storm. Among the proinflammatory cytokines, TNF-␣ and IFN-␥ are markedly elevated in patients with fatal CM (41). IL-1␤ is a pyrogenic cytokine that induces the production of prostaglandins, the major mediators of fever induction (42), and severe malaria has long been associated with high circulating levels of IL-1␤.…”

Medical genetics and genomic medicine in Nigeria

“…Nigerian populations were also included in subsequent studies such as genome-wide association studies (GWAS) or post-GWAS studies for various cardiometabolic disorders (Adeyemo et al, 2015;Chen et al, 2017;Kang et al, 2010;Nandakumar et al, 2017;Reder et al, 2012;Tayo, Luke, Zhu, Adeyemo, & Cooper, 2009;Tayo et al, 2013). Studies of host genetic risk factors for infectious disease have also been done in Nigerian populations, especially in relation to malaria (Amodu et al, 2005(Amodu et al, , 2012Olaniyan et al, 2014Olaniyan et al, , 2016, including some in the context of international consortia such as MalariaGen (Olaniyan et al, 2014;Clarke et al, 2017).…”

Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection

“…The area is a holo-endemic region characterized by yearround malaria transmission, with seasonal peaks between June-July and November-December [9]. In the study site, malaria presents as a range of sequelae ranging from mild presentation (uncomplicated malaria) to severe lifethreatening complications, such as severe malarial anaemia and cerebral malaria [7,9]. The sampling period was January-March 2016, a lower transmission season characterized by lower malaria incidence.…”

“…The sampling period was January-March 2016, a lower transmission season characterized by lower malaria incidence. Almost all the children recruited into this study (90%) were from the Yoruba ethnic group, the major ethnic group in the study area [7,9].…”

“…The heterozygous sickle haemoglobin genotype (HbAS) is the best-characterized human genetic polymorphism associated with malaria. The HbS allele has increased in frequency within the African population, hitting a prevalence of 25-30% in some African populations [7]. The high prevalence of HbS allele in sub-Saharan Africa and some other tropical areas is presumed to be due to the protection against severe malaria afforded to heterozygotes [8][9][10].…”