Evaluating the relationship between Clinical G6PD enzyme activity and gene variants

Area of Science:

• Biochemistry
• Genetics
• Hematology

Background:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent human enzyme disorder globally, often leading to intravascular hemolysis.
• Understanding the relationship between G6PD variants and enzyme activity is crucial for diagnosing and managing G6PD deficiency.

Purpose of the Study:

• To investigate the correlation between various Glucose-6-phosphate dehydrogenase (G6PD) genotypes and their corresponding enzyme activity levels in clinical blood samples.
• To quantify and compare the enzyme activity across different G6PD variants, including hemizygous, heterozygous, and compound heterozygous states.

Main Methods:

• Analysis of 15 distinct G6PD variants from 424 clinical blood samples.
• Utilized multicolor melting curve analysis and DNA sequencing to genotype G6PD variants.
• Measured G6PD enzyme activity levels (U/gHb) in the collected samples.

Main Results:

• Hemizygous deficient G6PD variants exhibited significantly lower enzyme activities (1.5-2.4 U/gHb) compared to heterozygous and compound heterozygous variants.
• Heterozygous G6PD enzyme levels ranged from 6.5-20.1 U/gHb with no significant differences among variants.
• Compound heterozygous mutations showed enzyme activity levels between 1.7-3.8 U/gHb, substantially lower than heterozygous states.
• The c.1024C > T (Chinese-5) mutation, affecting kinetic parameters, showed higher activity than other mutations in the β+α region.

Conclusions:

• A significant relationship exists between G6PD genotype and G6PD enzyme activity levels in blood.
• Genotyping provides valuable insights into the expected enzyme activity and potential clinical severity in G6PD deficiency.
• These findings support the use of molecular methods for characterizing G6PD variants and predicting enzyme function.