Authors: Au WY; Lam V; Pang A; Lee WM; Chan JL; Song YQ; Ma ES; Kwong YL
Abstract: BACKGROUND: Age-related skewing of X-chromosome inactivation leading to glucose-6-phosphate dehydrogenase (G6PD) deficiency in elderly women in a population with prevalent G6PD gene mutations was investigated. METHODS: G6PD activity was measured biochemically. G6PD mutations were detected by polymerase chain reaction (PCR) and allele-specific extension, and analyzed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and Sequenom MassARRAY. X-chromosome inactivation was quantified by semiquantitative PCR for the HUMARA gene, before and after HpaII digestion. RESULTS: In 173 women (median age: 90 years; range, 80-107 years), 18 heterozygotes for G6PD mutations were identified. Three heterozygotes were G6PD deficient, owing to skewed X-chromosome inactivation affecting the wild-type allele. Fifteen heterozygotes, with skewing apparently affecting the mutant alleles, had normal but significantly lower G6PD levels. At 1.73%, G6PD deficiency was significantly more frequent than expected from population screening at birth. CONCLUSION: Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.
Keywords: Aged; Aged, 80 and over; Aging/*metabolism; Cohort Studies; Female; Genotype; Glucosephosphate Dehydrogenase/genetics; Glucosephosphate Dehydrogenase Deficiency/*epidemiology/genetics; Humans; Mutation; Phenotype; X Chromosome Inactivation|
Journal: The journals of gerontology. Series A, Biological sciences and medical sciences Volume: 61 Issue: 10 Pages: 1086-9 Date: Nov. 2, 2006 PMID: 17077204 |
Au WY, Lam V, Pang A, Lee WM, Chan JL, Song YQ, Ma ES, Kwong YL (2006) Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians. The journals of gerontology. Series A, Biological sciences and medical sciences 61: 1086-9.
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