G6PD AND MTHFR GENE POLYMORPHISM: INTERACTION WITH OXIDATIVE STRESS, HB LEVELS AND RESPONSE TO IRON-FOLIC ACID + ALBENDAZOLE THERAPY IN MALNOURISHED CHILDREN

Abstract

Background: Polymorphisms in the G6PD and MTHFR genes have a significant impact on oxidative defense and folate metabolism which may alter how malnourished children respond to nutritional anemia treatment. However it is still unknown how they interact with iron-folic acid plus albendazole therapy.

Methodology: This quasi-experimental cross-sectional observational study was carried out at Tertiary Care Hospital Karachi between January and December of 2024. 150 malnourished children with anemia (Hb 11 g/dL) between the ages of 6 months and 12 years were included. Standardized iron-folic acid (3 mg/kg/day elemental iron + 1 mg folic acid) and a single dose of 400 mg of albendazole were given to the participants. Using PCR-RFLP G6PD and MTHFR C677T/A1298C polymorphisms were examined. Hemoglobin and oxidative stress markers (MDA GPx) were measured at baseline and 12 weeks.

Results:  MTHFR C677T polymorphism prevalence was 52% (heterozygous: 30% homozygous: 22%) and G6PD deficiency prevalence was 28% (heterozygous: 12% homozygous: 16%). In 38. 7% of participants combined polymorphisms were found. Overall mean hemoglobin increased from 8.4 ± 1.3 to 10.8 ± 1.5 g/dL however response differed significantly by genotype: no polymorphism (3.1 ± 0.9 g/dL) MTHFR-only (2.3 ± 1.0 g/dL) G6PD-only (1.7 ± 0.8 g/dL) and combined (1.0 ± 0.7 g/dL p = 0.001). The likelihood of a poor response was 8.4 times higher in children with combined polymorphisms (OR: 8. 4 95 percent CI:3.2 - 21.9). Children with G6PD deficiency had lower GPx (14.8 ± 4.2 vs. 20.1 ± 5.3 U/mL p = 0.001) and significantly higher baseline MDA (4.6 ± 1.2 vs. 3.4 ± 0.9 nmol/mL p = 0.001).

Conclusion: The hemoglobin response to conventional anemia treatment is severely hampered by G6PD and MTHFR polymorphisms with combined polymorphisms producing the most severe impairment. In order to optimize therapeutic outcomes for malnourished children and enable genotype-specific supplementation protocols genetic screening should be incorporated into pediatric anemia management.