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Infect Genet Evol. 2017 Nov;55:281-287. doi: 10.1016/j.meegid.2017.09.021. Epub 2017 Sep 19.

Marked variation in prevalence of malaria-protective human genetic polymorphisms across Uganda.

Author information

1
Infectious Diseases Research Collaboration, Kampala, Uganda.
2
London School of Hygiene and Tropical Medicine, London, United Kingdom.
3
Department of Medicine, University of California, San Francisco, CA, USA.
4
Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, Makerere University, Kampala, Uganda.
5
Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Pathology, Makerere University, Kampala, Uganda.
6
Department of Medicine, University of California, San Francisco, CA, USA. Electronic address: philip.rosenthal@ucsf.edu.

Abstract

A number of human genetic polymorphisms are prevalent in tropical populations and appear to offer protection against symptomatic and/or severe malaria. We compared the prevalence of four polymorphisms, the sickle hemoglobin mutation (β globin E6V), the α-thalassemia 3.7kb deletion, glucose-6-phosphate dehydrogenase deficiency caused by the common African variant (G6PD A-), and the CD36 T188G mutation in 1344 individuals residing in districts in eastern (Tororo), south-central (Jinja), and southwestern (Kanungu) Uganda. Genes of interest were amplified, amplicons subjected to mutation-specific restriction endonuclease digestion (for sickle hemoglobin, G6PD A-, and CD36 T188G), reaction products resolved by electrophoresis, and genotypes determined based on the sizes of reaction products. Mutant genotypes were common, with many more heterozygous than homozygous alleles identified. The prevalences (heterozygotes plus homozygotes) of sickle hemoglobin (28% Tororo, 25% Jinja, 7% Kanungu), α-thalassemia (53% Tororo, 45% Jinja, 18% Kanungu) and G6PD A- (29% Tororo, 18% Jinja, 8% Kanungu) were significantly greater in Tororo and Jinja compared to Kanungu (p<0.0001 for all three alleles); prevalences were also significantly greater in Tororo compared to Jinja for α-thalassemia (p=0.03) and G6PD A- (p<0.0001). For the CD36 T188G mutation, the prevalence was significantly greater in Tororo compared to Jinja or Kanungu (27% Tororo, 17% Jinja, 18% Kanungu; p=0.0004 and 0.0017, respectively). Considering ethnicity of study subjects, based on primary language spoken, the prevalence of mutant genotypes was lower in Bantu compared to non-Bantu language speakers, but in the Jinja cohort, the only study population with a marked diversity of language groups, prevalence did not differ between Bantu and non-Bantu speakers. These results indicate marked differences in human genetic features between populations in different regions of Uganda. These differences might be explained by both ethnic variation and by varied malaria risk in different regions of Uganda.

KEYWORDS:

CD36; G6PD; Malaria; Plasmodium; Sickle; Thalassemia

PMID:
28939159
PMCID:
PMC5685907
DOI:
10.1016/j.meegid.2017.09.021
[Indexed for MEDLINE]
Free PMC Article

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