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Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in the Middle East
B Kurdi-Haidar1, P J Mason, A Berrebi
1Department of Haematology, Royal Post-graduate Medical School, London, England.
Abstract:
A common glucose-6-phosphate dehydrogenase (G6PD) variant characterized by severe enzyme deficiency and B-like electrophoretic mobility is called "G6PD-Mediterranean" because it is found in different populations around the Mediterranean Sea. Sequence analysis of Italian subjects has revealed that the molecular basis of G6PD-Mediterranean is a single C-T transition at nucleotide position 563, causing a serine phenylalanine replacement at amino acid position 188. Most G6PD-Mediterranean subjects also have a silent C-T transition (without amino acid replacement) at nucleotide position 1311. Twenty-one unrelated individuals from Saudi Arabia, Iraq, Iran, Jordan, Lebanon, and Israel with both severe G6PD deficiency and B-like electrophoretic mobility were tested for both mutations by using amplification followed by digestion with appropriate restriction enzymes. All but one had the 563 mutation, and, of these, all but one had the 1311 mutation. Another 24 unrelated Middle Eastern individuals with normal G6PD activity or not known to be G6PD deficient were similarly tested. Four had the silent mutation at position 1311 in the absence of the deficiency mutation at position 563. We conclude that (1) the large majority of Middle Eastern subjects with the G6PD-Mediterranean phenotype have the same mutation found in Italy, (2) the silent mutation is an independent polymorphism in the Middle East, with a frequency of about .13, and (3) the mutation leading to the G6PD-Mediterranean deficiency has probably arisen on a chromosome that already carried the silent mutation.
Insights
The G6PD-Mediterranean variant, causing severe enzyme deficiency, is common in the Middle East. Most Middle Eastern patients share the same C-T mutation found in Italy, suggesting a shared origin.
Area of Science:
- Genetics
- Biochemistry
- Molecular Biology
Background:
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common genetic disorder.
- The G6PD-Mediterranean variant is characterized by severe enzyme deficiency and B-like electrophoretic mobility.
- This variant is prevalent in populations around the Mediterranean Sea.
Purpose of the Study:
- To investigate the molecular basis of the G6PD-Mediterranean variant in Middle Eastern populations.
- To determine the prevalence of specific G6PD mutations in individuals from Saudi Arabia, Iraq, Iran, Jordan, Lebanon, and Israel.
- To identify any independent genetic polymorphisms associated with G6PD activity in the region.
Main Methods:
- Sequence analysis of Italian subjects identified the G6PD-Mediterranean mutation as a C-T transition at nucleotide position 563 (Ser188Phe).
- A common silent C-T transition at nucleotide position 1311 was also noted in most G6PD-Mediterranean subjects.
- Amplification and restriction enzyme digestion were used to test for these mutations in Middle Eastern individuals.
Main Results:
- The majority of Middle Eastern subjects with the G6PD-Mediterranean phenotype possessed the 563 C-T mutation.
- Most individuals with the 563 mutation also carried the 1311 silent mutation.
- The 1311 silent mutation was found in some individuals without G6PD deficiency, indicating it is an independent polymorphism.
Conclusions:
- The G6PD-Mediterranean deficiency in the Middle East largely stems from the same mutation identified in Italy.
- The silent C-T transition at position 1311 is an independent genetic polymorphism in the Middle East with a frequency of approximately 13%.
- The G6PD-Mediterranean deficiency mutation likely arose on a chromosome already carrying the silent 1311 mutation.