title: Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals.
abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh.
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.
authors.forename: Suprovath Kumar
authors.initials: SK
authors.lastname: Sarker
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.
authors.forename: Md Tarikul
authors.initials: MT
authors.lastname: Islam
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.
authors.forename: Grace
authors.initials: G
authors.lastname: Eckhoff
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.
authors.forename: Mohammad Amir
authors.initials: MA
authors.lastname: Hossain
authors.affiliation: Department of Paediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, Singapore.
authors.forename: Syeda Kashfi
authors.initials: SK
authors.lastname: Qadri
authors.affiliation: Department of Virology, Institute of Epidemiology, Disease Control and Research, Mohakhali, Dhaka, Bangladesh.
authors.forename: A K M
authors.initials: AK
authors.lastname: Muraduzzaman
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.
authors.forename: Golam Sarower
authors.initials: GS
authors.lastname: Bhuyan
authors.affiliation: Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh.
authors.forename: Mohammod
authors.initials: M
authors.lastname: Shahidullah
authors.affiliation: Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh.
authors.forename: Mohammad Abdul
authors.initials: MA
authors.lastname: Mannan
authors.affiliation: Department of Paediatric Medicine, Dhaka Shishu Hospital, Dhaka, Bangladesh.
authors.forename: Sarabon
authors.initials: S
authors.lastname: Tahura
authors.affiliation: Department of Paediatric Medicine, Dhaka Shishu Hospital, Dhaka, Bangladesh.
authors.forename: Manzoor
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Department of Paediatrics, Bangladesh Institute of Research & Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Shahbag, Dhaka, Bangladesh.
authors.forename: Shahida
authors.initials: S
authors.lastname: Akhter
authors.affiliation: Department of Paediatrics, Bangladesh Institute of Research & Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Shahbag, Dhaka, Bangladesh.
authors.forename: Nazmun
authors.initials: N
authors.lastname: Nahar
authors.affiliation: Department of Virology, Institute of Epidemiology, Disease Control and Research, Mohakhali, Dhaka, Bangladesh.
authors.forename: Tahmina
authors.initials: T
authors.lastname: Shirin
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.|Department of Enteric and Respiratory Infectious Diseases, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Mohakhali, Dhaka, Bangladesh.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.affiliation: Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka, Bangladesh.
authors.forename: Kaiissar
authors.initials: K
authors.lastname: Mannoor
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001459:Bangladesh; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense
chemical_list: D005954:Glucosephosphate Dehydrogenase