Abstract
BackgroundThere are increasing evidences on the role of non-coding RNA (ncRNA) as key regulator of cellular homeostasis. LOC284889 is an uncharacterized ncRNA gene on reverse strand to MIF mapped to 22q11.23. MIF, a lymphokine, regulates innate immune response by up-regulating the expression of TLR4, suppressing the p53 activity and has been shown to be involved in malaria pathogenesis.MethodsIn this study, the possible effect of MIF variations on malaria susceptibility was investigated by re-sequencing the complete MIF gene along with 1 kb each of 5′ and 3′ region in 425 individuals from malaria endemic regions of the Orissa and Chhattisgarh states of India. The subjects comprised of 160 cases of severe malaria, 101 of mild malaria and 164 ethnically matched asymptomatic controls. Data were statistically compared between cases and controls for their possible association with Plasmodium falciparum malarial outcome.ResultsIt is the first study, which shows that the allele A (rs34383331T > A) in ncRNA is significantly associated with increased risk to P. falciparum malaria [severe: OR = 2.08, p = 0.002 and mild: OR = 2.09, P = 0.005]. In addition, it has been observed that the higher MIF-794CATT repeats (>5) increases malaria risk (OR = 1.61, p = 0.01). Further, diplotype (MIF-794CATT and rs34383331T > A) 5 T confers protection to severe malaria (OR = 0.55, p = 0.002) while 6A (OR = 3.07, p = 0.001) increases malaria risk.ConclusionsThese findings support the involvement of ncRNA in malarial pathogenesis and further emphasize the complex genetic regulation of malaria outcome. In addition, the study shows that the higher MIF-794CATT repeats (>5) is a risk factor for severe malaria. The study would help in identifying people who are at higher risk to malaria and adapt strategies for prevention and treatment.
Highlights
There are increasing evidences on the role of non-coding RNA as key regulator of cellular homeostasis
In conclusion, for the first time, this study reports the association of an ncRNA with malaria pathogenesis
This study observed that the MIF polymorphism is associated with malaria pathogenesis in Orissa and Chhattisgarh populations of India
Summary
There are increasing evidences on the role of non-coding RNA (ncRNA) as key regulator of cellular homeostasis. MIF, a lymphokine, regulates innate immune response by up-regulating the expression of TLR4, suppressing the p53 activity and has been shown to be involved in malaria pathogenesis. Cytokines plays crucial role as it speeds up the host inflammatory responses and coordinates the cell-mediated and humoral immune responses for the elimination and containment of invading microbes [12]. MIF (Macrophage migration inhibitory factor) is an important cytokine of host antimicrobial defense system, constitutively expresses with various other cytokines and promotes pro-inflammatory functions in both innate and acquired immunity [12,13]. It has been suggested that MIF regulates pro-inflammatory innate immune response by up regulating the expression of TLR4 and suppressing the p53 activity and the prolonged cell survival [16,17,19]
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