G6PD Deficiency and Hemoglobinopathies: Molecular Epidemiological Characteristics and Healthy Effects on Malaria Endemic Bioko Island, Equatorial Guinea.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies were the inherited conditions found mostly in African. However, few epidemiological data of these disorders was reported in Equatorial Guinea (EQG). This study aimed to assess the prevalence and healthy effects of G6PD deficiency and hemoglobinopathies among the people on malaria endemic Bioko Island, EQG.Blood samples from 4,144 unrelated subjects were analyzed for G6PD deficiency by fluorescence spot test (FST), high-resolution melting assay and PCR-DNA sequencing. In addition, 1,186 samples were randomly selected from the 4,144 subjects for detection of hemoglobin S (HbS), HbC, and α-thalassemia deletion by complete blood count, PCR-DNA sequencing and reverse dot blot (RDB).The prevalence of malaria and anemia was 12.6% (522/4,144) and 32.8% (389/1,186), respectively. Overall, 8.7% subjects (359/4,144) were G6PD-deficient by FST, including 9.0% (249/2,758) males and 7.9% (110/1,386) females. Among the 359 G6PD-deficient individuals molecularly studied, the G6PD A- (G202A/A376G) were detected in 356 cases (99.2%), G6PD Betica (T968C/A376G) in 3 cases. Among the 1,186 subjects, 201 cases were HbS heterozygotes, 35 cases were HbC heterozygotes, and 2 cases were HbCS double heterozygotes; 452 cases showed heterozygous α-thalassemia 3.7 kb deletion (-α3.7 kb deletion) and 85 homozygous - α3.7 kb deletion. The overall allele frequencies were HbS 17.1% (203/1186); HbC, 3.1% (37/1186); and -α3.7 kb deletion 52.4% (622/1186), respectively.High G6PD deficiency in this population indicate that diagnosis and management of G6PD deficiency is necessary on Bioko Island. Obligatory newborn screening, prenatal screening and counseling for these genetic disorders, especially HbS, are needed on the island

Evidence of positively selected G6PD A‐ allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island

Abstract Background Glucose‐6‐phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD‐deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting. Methods A case–control study was conducted on Bioko Island, Equatorial Guinea and further genotyping analysis used to detect natural selection of the G6PD A‐ allele. Results Our results showed G6PD A‐ allele could significantly reduce the risk of Plasmodium falciparum infection in male individuals (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.20–0.93; p < .05) and homozygous female individuals (AOR, 0.11; 95% CI, 0.01–0.84; p < .05). Additionally, the parasite densities were significantly different in the individuals with different G6PD A‐ alleles and individual levels of G6PD enzyme activity. The pattern of linkage disequilibrium and results of the long‐range haplotype test revealed a strong selective signature in the region encompassing the G6PD A‐ allele over the past 6,250 years. The network of inferred haplotypes suggested a single origin of the G6PD A‐ allele in Africans. Conclusion Our findings demonstrate that glucose‐6‐phosphate dehydrogenase (G6PD) A‐ allele could reduce the risk of P. falciparum infection in the African population and indicate that malaria has a recent positive selection on G6PD A‐ allele

Geographic location of the Bioko Island, Equatorial Guinea.

<p>Geographic location of the Bioko Island, Equatorial Guinea.</p

Genotyping of G6PD mutations (G202A and A376G) by high resolution melting (HRM) assay.

<p>The arrowhead indicates different genotypes. <b>A</b> and <b>C</b> are temp-shift melting cures; <b>B</b> and <b>D</b> are temp-shift difference melting plots. <b>A</b> and <b>B</b>: G202A mutation; <b>C</b> and <b>D</b>: A376G mutation.</p

The number and percentage of different deficient genotypes from our samples in both males and females.

<p>The number and percentage of different deficient genotypes from our samples in both males and females.</p