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The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in P. falciparum infection

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Abstract

To assess the hypothesis that nitric oxide (NO) is critical in the pathogenesis of cerebral malaria, we analyzed those single nucleotide polymorphisms (SNPs) and microsatellite (MS) of the promoter region of inducible nitric oxide synthase (iNOS) gene which are known to enhance the NO production in vivo. A total of 428 (204 severe, 224 mild) adult patients living in the eastern part of India were analyzed. The single nucleotide substitutions −954G→C was found to be very rare, and −1173C→T was absent in this population. But interestingly, longer forms of MS were found to be significantly associated with severe malaria (OR = 2.89, 95% CI = 1.955–4.295, P < 0.0001), and the linear regression analysis revealed that the risk of severe malaria significantly increases as the summed repeat number in an individual increase (OR = 1.16, P = 0.0013). Further, the median plasma level of nitrate/nitrite (NOx) was observed to be high in mild patients compared to severe patients, and the level of parasitemia was significantly low among mild patients than severe ones. These findings suggest that the CCTTT repeats in iNOS may play a key role in the pathogenesis of severe malaria.

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Acknowledgements

The authors thankfully acknowledge Indian Council of Medical Research, New Delhi for financial support and to the Director RMRC, Bhubaneswar for providing necessary laboratory facilities for the study. We also acknowledge Council of Scientific and Industrial Research, New Delhi for providing fellowship to Mr. G Dhangadamajhi to carry out the research work. The authors are grateful to the patients who participated in the study.

Conflicts of Interest

The authors have no conflicts of interest connecting to the work reported in this paper.

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Authors and Affiliations

  1. Regional Medical Research Centre (ICMR), Bhubaneswar, 751023, Orissa, India

    G. Dhangadamajhi, S. K. Kar & M. R. Ranjit

  2. SCB Medical College & Hospital, Cuttack, 753007, Orissa, India

    B. N. Mohapatra

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  1. G. Dhangadamajhi
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  2. B. N. Mohapatra
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  3. S. K. Kar
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  4. M. R. Ranjit
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Correspondence to M. R. Ranjit.

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Statement of authorship

G DhangdaMajhi: conducted laboratory analysis of samples and performed statistical analysis of the data, B N Mohaptra: selection and provision of treatment to the patients, S K Kar: clinicopathological analysis and interpretation of data, M R Ranjit: conception/design of the study, execution, and interpretation of the data and drafting the paper.

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Dhangadamajhi, G., Mohapatra, B.N., Kar, S.K. et al. The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in P. falciparum infection. Parasitol Res 104, 1315–1320 (2009). https://doi.org/10.1007/s00436-009-1329-9

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  • DOI: https://doi.org/10.1007/s00436-009-1329-9

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