Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population
Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population
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DOI：
10.1007/s00439-005-0126-5
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发表时间：
2006-06-01
期刊：
影响因子：
5.3
通讯作者：
Du, CS
中科院分区：
文献类型：
--
作者：
Jiang, WY;Yu, GL;Du, CS
对我国葡萄糖-6-磷酸脱氢酶（G6 PD）变异的结构和功能进行了系统研究。采用G6 PD/6PGD比值法对155，879名受试者进行G6 PD缺乏症筛查，共发现6，683例，患病率为0 ~ 17.4%。在知情同意的情况下，对来自11个族裔群体的1 004例病例进行了分子分析。我们的研究结果表明：（1）中国人群中G6 PD变异在传统的种族界限上是一致的，但在基于种族的群体中频率不同;（2）中国人群中的G6 PD变异与非洲、欧洲和印度人群中的G6 PD变异不同;（3）发现了一种新的G6 PD缺陷突变，274 C-> T，（4）变性高效液相色谱法检测G6 PD缺陷型突变对诊断和遗传咨询具有重要意义。此外，人G6 PD变体的功能分析显示以下：（2）G6 PDArg 459和Arg 463在NADP（+）锚定到催化结构域以维持酶活性方面起重要作用，（3）从密码子459到羧基端的序列是酶功能所必需的。
A systematic study on the structure and function of Glucose-6-phosphate dehydrogenase (G6PD) variations was carried out in China. A total of 155,879 participants were screened for G6PD deficiency by the G6PD/6PGD ratio method and 6,683 cases have been found. The prevalence of G6PD deficiency ranged from 0 to 17.4%. With informed consent, 1,004 cases from 11 ethnic-based groups were subjected to molecular analysis. Our results showed the followings: (1) The G6PD variants are consistent across traditional ethnic boundaries, but vary in frequencies across ethnic-based groups in Chinese population, (2) The G6PD variants in Chinese population are different from those in African, European, and Indian populations, (3) A novel G6PD-deficiency mutation, 274C -> T, has been found, and (4) Denaturing high performance liquid chromatography is of great advantage to detecting G6PD-deficient mutations for diagnosis and genetic counseling. Moreover, functional analysis of the human G6PD variants showed the following: (1) The charge property, polarity, pK-radical and side-chain radical of the substituting amino acid have an effect on G6PD activity, (2) The G6PDArg459 and Arg463 play important roles in anchoring NADP(+) to the catalytic domain to maintain the enzymatic activity, and (3) The sequence from codon 459 to the carboxyl terminal is essential for the enzymatic function.