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Background  There 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.    Methods  In 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.    Results  It is the first study, which shows that the allele  A  (rs34383331 T > 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 rs34383331 T > 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.    Conclusions  These 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.

Variations in ncRNA gene LOC284889 and MIF-794CATT repeats are associated with malaria susceptibility in Indian populations