Polymorphisms of Nitric Oxide Synthase-2 Gene Among Different Ethnic Groups in Malaria Endemic Areas in Eastern Sudan

Abstract

Ongoing and previous studies in eastern Sudan (in Koka and Umsalala villages), inhabited by two different ethnic groups, Hausa and Masalit respectively, showed a great variation in the prevalence of malaria despite the same epidemiological setup. These differences might be in consequence of host genetic factors. The purpose of this study is to investigate the frequency of NOS2A promoter polymorphisms which has a known association with malaria phenotypes, in Hausa and Masalit populations. Three different single nucleotide polymorphisms in the promoter region of NOS2 gene were screened: NOS2 –954G/C, –1173C/T, and - 1659C/T by using RFLP, ARMS- PCR and iPLEX™ assay respectively. There was no difference in minor allele frequency of NOS2A SNPs in parents and unrelated individuals in the two populations but significant higher frequency of NOS2-954C and -1659T in Hausa children when compared with Masalit. Compared with European and Asian populations, the data was showed higher frequencies of NOS2A polymorphisms. Only the marker -1173C/T was found to be deviated from Hardy Weinberg equilibrium in Hausa population. NOS2 –1173 T allele reduced the risk of symptomatic malaria in Tanzanian children and that of severe malarial anaemia in Kenya. This DHWE in -1173C/T may explain that the asymptomatic malaria in Hausa may be due to natural selection. Our Haplotypes frequency showed marginal variation between the two populations. However, only (CCC) showed significant increase in Masalit rather than Hausa. In this study complete linkage disequilibrium was found between pairs of alleles of -1173C\T with both -1659C\T and -954G\C in Hausa population. By contrast this high LD was not detected in Masalit population, where -1659C\T showed complete LD only with -954G\C. NOS2A promoter region was insignificantly deviated from the selection neutrality using Tajima’s D test and all Tajima's D values were negative in the two populations which indicate a selective sweep. This variation in alleles and haplotypes frequencies among the two ethnic groups, may explain the different pattern of malaria phenotype in those populations but further genetic association studies is needed.