Prevalence of CYP2D6 Genotypes and Predicted Phenotypes in a Cohort of Cambodians at High Risk for Infections with Plasmodium vivax.

Abstract

Clinical failure of primaquine (PQ) has been demonstrated in people with CYP450 2D6 genetic polymorphisms that result in reduced or no enzyme activity. The distribution of CYP2D6 genotypes and predicted phenotypes in the Cambodian population is not well described. Surveys in other Asian countries have shown an approximate 50% prevalence of the reduced activity CYP2D6 allele *10, which could translate into increased risk of PQ radical cure failure and repeated relapses, making interruption of transmission and malaria elimination difficult to achieve. We determined CYP2D6 genotypes from 96 volunteers from Oddor Meanchey Province, Cambodia, an area endemic for Plasmodium vivax. We found a 54.2% frequency of the *10 allele, but in approximately half of our subjects, it was paired with a normal activity allele, either *1 or *2. The prevalence of *5, a null allele, was 9.4%. Overall predicted phenotype percentages were normal metabolizers, 46%; intermediate metabolizers, 52%; and poor metabolizers, 1%.

• Authors: Michele D Spring, Chanthap Lon, Somethy Sok, Darapiseth Sea, Mariusz Wojnarski, Soklyda Chann, Worachet Kuntawunginn, Thay Kheang Heng, Samon Nou, Montri Arsanok, Sabaithip Sriwichai, Pattaraporn Vanachayangkul, Jessica T Lin, Jessica E Manning, Krisada Jongsakul, Sathit Pichyangkul, Prom Satharath, Philip L Smith, Lek Dysoley, David L Saunders, Norman C Waters
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 103 Issue 2 Pg. 756-759 (08 2020) ISSN: 1476-1645 [Electronic] United States
• PMID: 32394887 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antimalarials
• Artemisinins
• Quinolines
• artenimol
• piperaquine
• Cytochrome P-450 CYP2D6
• Primaquine

Topics

• Antimalarials (therapeutic use)
• Artemisinins (therapeutic use)
• Asian People (genetics)
• Cambodia
• Cytochrome P-450 CYP2D6 (genetics)
• Drug Therapy, Combination
• Endemic Diseases
• Gene Frequency
• Genotype
• Humans
• Malaria, Vivax (drug therapy)
• Pharmacogenomic Variants
• Phenotype
• Plasmodium vivax
• Polymorphism, Genetic
• Primaquine (therapeutic use)
• Quinolines (therapeutic use)
• Recurrence
• Treatment Failure