Table 2.
Polymorphic G6PD variants and haplotypes associated with drug response
| Variants genotyped | Drug or treatment | Associated response | Referencea |
|---|---|---|---|
| A-Haplotype | |||
| 202A/376G (rs1050828 and rs1050829) | Glibenclamide | Acute hemolysis | [93] (case study) |
| 202A (rs1050828) | Sulfadoxine-pyrimethamine and artemisinin and primaquine | Increased risk of developing moderate anemia | [66]b n = 562 total population genotyped, 8.4% heterozygous, 3.9% homozygous/ hemizygous. |
| 202A (rs1050828) | Chlorproguanil-dapsone (CD) | Increased risk of a drop in hemoglobin levels, compared with sulfadoxine-pyrimethamine (SP) treatment | [65] (n = 1480 total study group treated with CD, n = 370 treated with SP. n = 237 treated with CD had a > 20 g/L decrease in hemoglobin and of these 35% were carriers of this variant, defined as G6PD deficient), compared with 24% treated with SP |
| 202A (rs1050828) | Chlorproguanil-dapsone-artesunate | Severe decreases in hemoglobin levels and increased risk of blood transfusion | [69] 13% were carriers of this variant and defined as A- G6PD deficient, in n = 343 total genotyped. |
| 202A (rs1050828) | Sulphadoxine-pyrimethamine coadministered with amodiaquine | Increased risk of requiring a blood transfusion | [69] 11% were carriers of this variant and defined as A- G6PD deficient in n = 359 total genotyped. |
| 202A (rs1050828) | Chlorproguanil-dapsone-artesunate | Severe reduction in hemoglobin levels and an increased risk of requiring a blood transfusion | [68] n = 800 genotyped. G6PD-deficient individuals were defined as A- hemizygous men (17% of n = 388), and homozygous A-/ A- women (4% of n = 412) |
| 376G (rs1050829) | |||
| 680T (rs137852328) | |||
| 968C (rs76723693) | |||
| 542G (rs5030872) | |||
| NS | Rasburicase | Hemolytic anemia | [84] (case study) |
| NS | Daunorubicin | Reduced drug metabolism | [87] (in vitro) |
| NS | Methylene blue | Hemolysis in an individual with methemoglobinemia | [94] (case study) |
| NS | Vitamin C (high dose of 80 g intravenously, 2 days) | Hemolysis | [95] (case study) |
| Mediterranean variant | |||
| 563T (rs5030868) | Glibenclamide | Acute hemolysis | [92] (case study) |
| NS | Aspirin (high dose of 100 mg/kg daily) | Severe hemolytic anemia in a child with systemic arthritis | [88] (case study) |
| NS | Daunorubicin | Reduced drug metabolism | [87] (in vitro) |
| NS | Rasburicase | Severe G6PD deficiency was revealed during treatment | [86] (case study) |
NS, not specified.
For each reference, details of whether the study was a single case study, or total study numbers and percentage of individuals carrying the indicated G6PD allele, are given in the reference column – see www.pharmgkb.org website for further annotations of these studies. The G6PD gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, and therefore, the alleles on the website will differ (in a complementary manner) from those in this review that are given on the minus strand as reported in the literature.
Please note that in this study, heterozygous 202A individuals were considered as G6PD A, and hemizygous/ homozygous 202A individuals were classified as G6PD A-.