Article

Intervillous macrophage migration inhibitory factor is associated with adverse birth outcomes in a study population in central India.

National Institute of Malaria Research Field Unit, Jabalpur, Madhya Pradesh, India.
PLoS ONE (Impact Factor: 3.53). 12/2012; 7(12):e51678. DOI: 10.1371/journal.pone.0051678
Source: PubMed

ABSTRACT Macrophage migration inhibitory factor (MIF) is a pluripotent factor produced by a variety of cells. It plays an important biological role in the regulation of pregnancy and has been shown to influence malaria pathogenesis. In this study, the levels of MIF in the peripheral, cord and placental intervillous blood (IVB) plasma collected from women residing in a malaria endemic region of Central India was determined and its association with malaria in pregnancy and birth outcomes was investigated. MIF levels were significantly different in IVB, peripheral, and cord plasma, with IVB plasma having the highest MIF levels and peripheral plasma having the lowest. Placental malaria positive women had significantly higher IVB plasma MIF levels than placental malaria negative women, but this relationship was not seen in peripheral or cord plasma MIF levels. In addition, the odds of stillbirth and low birth weight deliveries for the uppermost placental MIF quartile (irrespective of placental malaria status) was significantly higher than that of the lowest placental MIF quartile, supporting the hypothesis that elevated concentrations of placental MIF may be associated with an increased risk of adverse birth outcome.

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    ABSTRACT: 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. 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[prime] and 3[prime] 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. It 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. 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.
    Malaria Journal 09/2013; 12(1):345. DOI:10.1186/1475-2875-12-345 · 3.49 Impact Factor

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