Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population

• Published in: Human genetics Vol. 119; no. 5; pp. 463 - 478
• Main Authors: Jiang, Weiying, Yu, Guolong, Liu, Peng, Geng, Qian, Chen, Luming, Lin, Qundi, Ren, Xiaoqin, Ye, Wenhong, He, Yongshu, Guo, Yibin, Duan, Shan, Wen, Jing, Li, Haiyuan, Qi, Yan, Jiang, Chengrui, Zheng, Yongmei, Liu, Chun, Si, En, Zhang, Qin, Tian, Qiuhong, Du, Chuanshu
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.06.2006; Berlin Springer Nature B.V; New York, NY
• Subjects: Amino Acid Substitution - genetics; Anemia; Arginine - genetics; Biological and medical sciences; China; Chromatography; Classical genetics, quantitative genetics, hybrids; Dehydrogenases; Enzymes; Female; Fundamental and applied biological sciences. Psychology; Genetic counseling; Genetic Testing; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Glucose; Glucosephosphate Dehydrogenase - chemistry; Glucosephosphate Dehydrogenase - genetics; Glucosephosphate Dehydrogenase - physiology; Glucosephosphate Dehydrogenase Deficiency - diagnosis; Glucosephosphate Dehydrogenase Deficiency - enzymology; Glucosephosphate Dehydrogenase Deficiency - genetics; Glycogen Storage Disease Type I - enzymology; Glycogen Storage Disease Type I - genetics; Human; Humans; Male; Mutation; NADP - metabolism; Protein Structure, Secondary - genetics; Structure-Activity Relationship; China; Yunnan China; Variant; Glucose-6-phosphate 1-dehydrogenase; Enzyme; Chinese; Genetics; Population; Oxidoreductases; Structure
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-005-0126-5

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.