Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population.
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.
Jiang
Weiying
W
Department of Medical Genetics, Medical School, Sun Yat-sen University, Guangzhou, China, jweiying@hotmail.com
Yu
Guolong
G
Liu
Peng
P
Geng
Qian
Q
Chen
Luming
L
Lin
Qundi
Q
Ren
Xiaoqin
X
Ye
Wenhong
W
He
Yongshu
Y
Guo
Yibin
Y
Duan
Shan
S
Wen
Jing
J
Li
Haiyuan
H
Qi
Yan
Y
Jiang
Chengrui
C
Zheng
Yongmei
Y
Liu
Chun
C
Si
En
E
Zhang
Qin
Q
Tian
Qiuhong
Q
Du
Chuanshu
C
D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D002681:China; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D009249:NADP / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000235:genetics; D013329:Structure-Activity Relationship
D009249:NADP; D001120:Arginine; D005954:Glucosephosphate Dehydrogenase