University of Khartoum

Candidate Malaria Susceptibility /Protective SNPs in Hospital and Population Based Studies; the Effect of Sub Structuring

Candidate Malaria Susceptibility /Protective SNPs in Hospital and Population Based Studies; the Effect of Sub Structuring

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Title: Candidate Malaria Susceptibility /Protective SNPs in Hospital and Population Based Studies; the Effect of Sub Structuring
Author: Ahmed, Nahid Awad Alseaid Eid
Abstract: Objectives: The aim of this study to address the possible impact of population stratification on the outcome of case control studies in different population. A population based study was carried out in Koka and Salala villages in eastern Sudan, while a hospital based study was conducted in Sinnar area in Central Sudan. Materials and Methods: 72 SNPs were genotyped using iPLEX technology in 400 DNA samples that included the two village populations, malaria patients and out-patients from Sinnar in addition to control consisting of healthy Nilo-Saharan speaking individuals. Results: The Hardy Weinberg values were within expectation for 8 and 6 SNPs out of 25 in Hausa and Massalit respectively. However DHWE was observed in 9 out of 25 SNPs in Sinnar area but not for those that were differentially distributed between malaria cases and controls. Most of the DHWE in Sinnar was due to excess of homozygote which is explained by the Whalund effect. The program structure reveals the division of both Hausa and Massalit into tow substructure, the substructure in Hausa was more supported in two compact clusters, while in Massalit was more distributed in clustering. In Sinnar the Structure results also does not resolves defined substructure. More than 25 SNPs and variants were informative in all areas, including alpha thalassemia 3.7 deletion which has been genotyped for the first time in Sudan in a different cohort of samples from the two villages. DHWE (p= 0.043) was evident among Hausa in the form of deficient homo mutant of the deletion. Some important SNPs were not differentially distributed between malaria cases and controls, including SNPs in CD36 and iNOS. Interestingly six SNPs showed significant p-values for differences in distribution between cases and controls: IL4R (p= 0.001), CR1 (p= 0.02) and TNF (p= 0.01) in hospital samples. In Massalit: IL10 (p= 0.04) and G6PD (p= 0.02), IL4 590 (p= 0.04) in Hausa. The differences for malaria status between and within the two villages may be due to such differences in the immune response that is in turn is an outcome of the difference in the population genetics structure. We find highly significant p values for three polymorphisms TNF, IL4R, CR1 in the hospital samples. Those SNPs had already been associated with protection/susceptibility to severe malaria which conforms to the nature of the study being on outpatients. Conclusion: In this study the substructure of the population had no impact on the malaria distribution in Hausa, while in the Massalit where malaria cases were mostly in the single major cluster, the removal of the minor cluster had changed the significance of association. This is probably the first study to implicate in a direct manner the genetic population structure to malaria susceptibility. Malaria susceptibility/protection genes as polymorphic traits are showing variations in allele and genotype frequencies in different populations that often correlate with the malaria phenotype. There was no single protective /susceptibility polymorphism across samples. Population Structure has significant impact at the population, area, village and possibly familial levels in susceptibility to malaria
Description: 102 Pages
URI: http://khartoumspace.uofk.edu/123456789/25346


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