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G6PD Namoru (208 T→ C) is the major polymorphic variant in the tribal populations in southern India

2006; Wiley; Volume: 136; Issue: 3 Linguagem: Inglês

10.1111/j.1365-2141.2006.06463.x

1365-2141

Rati Chalvam, Malay B. Mukherjee, Roshan Colah, D. Mohanty, Kanjaksha Ghosh,

Erythrocyte Function and Pathophysiology

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythroenzymopathy among humans, affecting over 400 million people worldwide, and is characterised by considerable biochemical and molecular heterogeneity (Beutler, 1996). The Indian population is unique, comprising of numerous caste and tribal groups each with a characteristic physical, cultural and genetic background. The tribes practice strict endogamy and may be considered a genetic isolate. G6PD deficiency was reported in India more than 40 years ago and the prevalence varies from 5.7% to 27.9% in different caste and tribal groups (Sukumar et al, 2004). However, there is scanty information about the molecular basis of G6PD deficiency among the tribal Indian population. We report the mutations causing G6PD deficiency among four tribal groups originating from the Nilgiri district of Tamilnadu, southern India. The prevalence of G6PD deficiency in these groups varied from 0.7% to 10.6% with an overall prevalence of 5.4% (Table I). Mutational analysis could be performed on 40 G6PD-deficient males. All the samples were first screened for the G6PD Orissa (131C→G) mutation by HaeIII digestion and it was observed that the expected 107 bp band was absent in 28 (70.4%) of the G6PD-deficient individuals. DNA sequencing of these samples revealed a T → C substitution at position 208 in exon 4, resulting in the substitution of histidine to tyrosine at amino acid 70, which corresponds to G6PD Namoru. Creation of an NlaIII restriction site further confirmed the presence of this mutation. The remaining 12 samples were screened for the G6PD Kerala–Kalyan (949 G →A) and the G6PD Mediterranean (563 C →T) mutations. Five individuals showed the presence of the G6PD Kerala–Kalyan mutation (12.5%) while G6PD Mediterranean was absent. Seven samples remained uncharacterised. G6PD Namoru (amino acid 70) is located in exon 4 of the G6PD gene and is in close proximity to the mutation at amino acid 68, which if present together, causes it to become the G6PD A-variant. This is a very rare variant and has thus far been reported only in three G6PD-deficient individuals from the Vanuatu Archipelago (Southwestern Pacific) (Ganczakowski et al, 1995). In our study, the G6PD Namoru mutation was found in three of the tribal groups and can be considered the most common polymorphic variant in the tribal groups from the Nilgiris in Tamilnadu (South India). This probably indicates that G6PD Namoru might have originated in South India and subsequently spread to Vanuatu during human migration from Africa to Australia along the coast of southern India (Pitchappan, 2003). G6PD Kerala–Kalyan, a mutation in exon 9 of the G6PD gene has been reported from Maharashtra (west), Kerala (south), Punjab (north) and amongst Indo-Mauritians ascertained to be from Andhra Pradesh and Tamilnadu in southern India (Kotea et al, 1999). This mutation was present in a low frequency in all the four tribal groups studied here. Earlier reports showed that this mutation was absent in the tribal groups from Orissa and Madhya Pradesh (Kaeda et al, 1995). Thus, G6PD Namoru is the predominant mutation causing G6PD deficiency in tribal groups of the Nilgiri hills and is being reported for the first time in the Indian population. Our study also differs from earlier observations that G6PD Orissa is the major polymorphic variant among the tribes of India (Kaeda et al, 1995).