Exploring the association between glucose-6-phosphate dehydrogenase deficiency and color blindness in Southeast Asia

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency poses problems for the treatment of Plasmodium vivax malaria, as the 8-aminoquinolines, used to eliminate liver hypnozoites, cause hemolysis in G6PD-deficient individuals. G6PD deficiency is an X-linked disorder that can be linked to other conditions determined by genes located nearby on the Xq28 band of the X chromosome, including red-green color blindness. A Karen population has undergone recent positive selection for G6PD deficiency with extended long-range haplotypes around G6PD. Objectives: To determine the association between G6PD deficiency and color blindness in a Karen population that lives in an area endemic for P. vivax and that is already known to display long-range haplotypes around G6PD because of the recent positive selection of the Mahidol G6PD deficiency allele. Method: We examined the phenotypic association between G6PD deficiency and color blindness. Results: Of 186 male participants successfully assessed for color blindness using the Ishihara 38 plates test, 10 (5.4%) were red-green color blind, while 1 individual was totally color blind. There was a nonsignificant trend toward negative association (repulsion) between G6PD deficiency and red-green color blindness; 34/35 individuals with the Mahidol variant of G6PD deficiency had normal vision, while 9 of the 10 red-green color blind individuals were G6PD normal. A single individual had both conditions. Conclusions: Despite the long-range haplotype associated with G6PD deficiency in this population, color blindness is not informative in terms of predicting G6PD deficiency in this population. The most likely explanation is that there are multiple genetic causes of red-green color blindness.