1. Prevalence of Human Genetic Polymorphisms Associated with Protection from Malaria in Regions of Uganda with Different Levels of Malaria Endemicity
Moses Kiggundu1, Andrew Walakira1, Federica Verra3, Patrick Kakeeto1, Stephen Tukwasibwe1, Emmanuel Ruhamyankaka1, Chris Drakeley3, Grant Dorsey2, Moses Kamya1, Samuel L. Nsobya1, Philip J. Rosenthal2
1Infectious Diseases Research Collaboration, Kampala, Uganda, 2 University of California, San Francisco, USA, 3 London School of Hygiene and Tropical Medicine
Introduction
Table showing summary of results
Results
Mutations in several human genes have been associated with protection against malaria, including the sickle hemoglobin mutation (E6V in the globin gene), the α-thalassemia 3.7kb deletion, a common African variant of the gene encoding glucose-6-phosphate dehydrogenase (G6PD A-), and the CD36 T188G mutation. We hypothesized that the prevalence of genetic polymorphisms that are protective against malaria would be lower in regions of Uganda with lower compared to higher malaria endemicity.
Site
No. of samples with results
Wild type (%)
Heterozygous + Homozygous (%)
Chi sq test p-value
HbS
Jinja
429
320 (75)
109 (25)
Kanungu
458
427 (93)
31 (7)
<
Tororo
434
313 (72)
121 (28)
Alpha Thal
430
236 (55)
194 (45)
440
362 (82)
78 (18)
414
196 (47)
218 (53)
G6PD
432
355 (82)
77 (18)
453
418 (92)
35 (8)
438
310 (71)
128 (29)
CD36 T188G
433
360 (83)
73 (17)
459
377 (82)
82 (18)
442
324 (73)
118 (27)
The prevalences of the sickle hemoglobin mutation (28% Tororo, 25% Jinja, 7% Kanungu), the α-thalassemia 3.7 kb deletion (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 (chi square p< for all 3 alleles). For the CD36 T188G mutation (27% Tororo, 17% Jinja, 18% Kanungu), the prevalence was significantly greater in Tororo compared to Kanugu and Jinja( p<0.0001).
Methods
1,344 subjects were enrolled in cohorts from Kanungu, Jinja, and Tororo Districts, with historically low, moderate, and high malaria endemicity, respectively. DNA was extracted from buffy coat samples using a Qiagen kit. Genes of interest were amplified with PCR (nested where applicable). Amplicons were subjected to mutation-specific restriction. endonuclease digestion (for sickle cell, G6PD A-, and CD36 T188G). Reaction products were resolved by agarose gel electrophoresis.
Map of Uganda showing location of study sites
Summary and Conclusions
Tororo
Jinja
The prevalence of malaria protective polymorphisms varied across Uganda and was greatest in areas with historically high levels of malaria transmission. Our data are consistent with the hypothesis that the evolutionary pressure of lethal malaria selected for these polymorphisms. .
Kanungu
Table showing difference in prevalence of polymorphisms between Kanungu compared with Jinja and Tororo. Chi square test was used to test the differences.