Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians
Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians
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DOI：
10.1093/gerona/61.10.1086
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发表时间：
2006-10-01
影响因子：
5.1
通讯作者：
Kwong, Yok-Lam
中科院分区：
文献类型：
--
作者：
Au, Wing-Yan;Lam, Veronica;Kwong, Yok-Lam
背景资料。在葡萄糖-6-磷酸脱氢酶(G6PD)基因突变盛行的人群中，研究了X染色体失活导致老年女性G6PD缺乏症的年龄相关性偏斜。生化方法测定G6PD活性。采用聚合酶链式反应和等位基因特异性延伸技术检测G6PD基因突变，并用基质辅助激光解吸电离飞行时间质谱仪和Sequenom Massarray进行分析。在HpaII消化前后，用半定量聚合酶链式反应检测HUMARA基因的X染色体失活。在173名女性(中位年龄：90岁，范围为80-107岁)中，鉴定出18个G6PD突变杂合子。3个杂合子G6PD缺乏，这是由于X染色体的偏斜失活影响了野生型等位基因。15个杂合子，倾斜明显影响突变等位基因，具有正常但显著降低的G6PD水平。G6PD缺乏症的发生率为1.73%，明显高于出生时人群筛查的预期。由于X染色体倾斜失活，在G6PD突变普遍的人群中，老年妇女面临G6PD缺乏症的风险。
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 alletes, 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.