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Infection and Immunity, July 2009, p. 2943-2947, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00083-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Endothelial Nitric Oxide Synthase Gene Polymorphisms and Plasmodium falciparum Infection in Indian Adults {triangledown}

Gunanidhi Dhangadamajhi,1 Biranchi N. Mohapatra,2 Shantanu K. Kar,1 and Manoranjan Ranjit1*

Regional Medical Research Centre (ICMR), Bhubaneswar 751023, Orissa, India,1 SCB Medical College & Hospital, Cuttack 753007, Orissa, India2

Received 22 January 2009/ Returned for modification 2 March 2009/ Accepted 1 April 2009

To explore the hypothesis that susceptibility to cerebral malaria is influenced by genetic variation in endothelial nitric oxide synthase (eNOS), we genotyped three commonly defined polymorphic loci of eNOS, Glu298->Asp, intron 4 variable number of tandem repeat region, and T-786->C, in 244 patients (mean age, 36.2 years) with mild malaria and 194 patients (mean age, 35.6 years) with severe malaria belonging to same ethnic group in Orissa, an eastern Indian state. We found that there was an association of the Glu298->Asp substitution (P = 0.0037; odds ratio, 1.95; 95% confidence interval, 1.2 to 3.0) and a single unique haplotype defined by "C-b-Asp" (Pcorrected = 0.0024) for protection against cerebral malaria. Further, the median plasma level of nitrite-nitrate was found to be increased in individuals with the Glu298->Asp substitution and was significantly higher in the mild malaria group (P ≤ 0.0001), but the increase was not significant in the severe malaria group (P = 0.0528). These findings suggest that the Glu298->Asp substitution and the "C-b-Asp" haplotype may enhance eNOS expression and NO production, which leads to protection against cerebral malaria. These findings may increase our understanding of the pathogenesis of malaria.

* Corresponding author. Mailing address: Regional Medical Research Centre, Indian Council of Medical Research, Chandrasekharpur, Bhubaneswar 751023, Orissa, India. Phone: 91-943-7488192. Fax: 91-674-2301351. E-mail: ranjit62{at}gmail.com

{triangledown} Published ahead of print on 13 April 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, July 2009, p. 2943-2947, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00083-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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