title: Prevalence and molecular characterization of G6PD deficiency in two Plasmodium vivax endemic areas in Venezuela: predominance of the African A-(202A/376G) variant.
abstract: BACKGROUND
  Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes acute haemolytic anaemia triggered by oxidative drugs such as primaquine (PQ), used for Plasmodium vivax malaria radical cure. However, in many endemic areas of vivax malaria, patients are treated with PQ without any evaluation of their G6PD status.
  
  
  METHODS
  G6PD deficiency and its genetic heterogeneity were evaluated in northeastern and southeastern areas from Venezuela, Cajigal (Sucre state) and Sifontes (Bolívar state) municipalities, respectively. Blood samples from 664 randomly recruited unrelated individuals were screened for G6PD activity by a quantitative method. Mutation analysis for exons 4-8 of G6PD gen was performed on DNA isolated from G6PD-deficient (G6PDd) subjects through PCR-RFLP and direct DNA sequencing.
  
  
  RESULTS
  Quantitative biochemical characterization revealed that overall 24 (3.6%) subjects were G6PDd (average G6PD enzyme activity 4.5 ± 1.2 U/g Hb, moderately deficient, class III), while DNA analysis showed one or two mutated alleles in 19 of them (79.2%). The G6PD A-(202A/376G) variant was the only detected in 17 (70.8%) individuals, 13 of them hemizygous males and four heterozygous females. Two males carried only the 376A → G mutation. No other mutation was found in the analysed exons.
  
  
  CONCLUSIONS
  The G6PDd prevalence was as low as that one shown by nearby countries. This study contributes to the knowledge of the genetic background of Venezuelan population, especially of those living in malaria-endemic areas. Despite the high degree of genetic mixing described for Venezuelan population, a net predominance of the mild African G6PD A-(202A/376G) variant was observed among G6PDd subjects, suggesting a significant flow of G6PD genes from Africa to Americas, almost certainly introduced through African and/or Spanish immigrants during and after the colonization. The data suggest that 1:27 individuals of the studied population could be G6PDd and therefore at risk of haemolysis under precipitating factors. Information about PQ effect on G6PDd individuals carrying mild variant is limited, but since the regimen of 45 mg weekly dose for prevention of malaria relapse does not seem to be causing clinically significant haemolysis in people having the G6PD A-variant, a reasoned weighing of risk-benefit for its use in Venezuela should be done, when implementing public health strategies of control and elimination.
authors.affiliation: Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo 21827, Caracas, 1020-A, Venezuela. esmeralda.vizzi@gmail.com.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Vizzi
authors.affiliation: Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo 21827, Caracas, 1020-A, Venezuela. bastidasprotozoo@hotmail.com.|Laboratorio de Inmunoparasitología, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo 21827, Caracas, 1020-A, Venezuela. bastidasprotozoo@hotmail.com.|Departamento de Salud Pública, Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Edo. Carabobo, Venezuela. bastidasprotozoo@hotmail.com.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Bastidas
authors.affiliation: Laboratorio de Inmunoparasitología, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo 21827, Caracas, 1020-A, Venezuela. mariana.hidalgo.r@gmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Hidalgo
authors.affiliation: Laboratorio de Inmunoparasitología, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo 21827, Caracas, 1020-A, Venezuela. laura.colman@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Colman
authors.affiliation: Laboratorio de Inmunoparasitología, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Apdo 21827, Caracas, 1020-A, Venezuela. hildaper@gmail.com.
authors.forename: Hilda A
authors.initials: HA
authors.lastname: Pérez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000235:genetics* / Q000472:pathogenicity*; D014687:Venezuela / Q000453:epidemiology; D055815:Young Adult