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

Abstract

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.

Further investigations of glucose-6-phosphate dehydrogenase variants in Flores Island, eastern Indonesia

“…In contrast, G6PD Canton, another common variant in Chinese population, was never seen in the Sikka nor in the Ende. Many surveillances of G6PD deficiency in Chinese, Thai, and Malay populations, conducted in China, Taiwan, Thailand, Malaysia and Singapore, have revealed that frequency of G6PD Canton is higher than that of G6PD Kaiping (Chang et al 1992;Huang et al 1996;Chiang et al 1999;Ainoon et al 1999;Nuchprayoon et al 2002) or they are almost equal (Chiu et al 1993;Quak et al 1996;Ainoon et al 2003Ainoon et al , 2004Jiang et al 2005Jiang et al , 2006. Therefore, it is interesting why G6PD Canton was not detected in the Sikka or Ende populations.…”

Phylogeny and Origin of Glucose-6-Phosphate Dehydrogenase (G6PD) Defi ciency Mutations in Indonesia

“…The high frequency distribution of G6PD Kaiping, a common variant in Chinese population, in the Sikka, Flores Islands is a rather unexpected fi nding (Kawamoto et al, 2006). In contrast, Jiang et al (2006) characterized that G6PD Canton was never seen in the Sikka, Flores Islands nor in the Ende, Timor Islands, although many studies revealed that G6PD Canton in China, Taiwan, Thailand, Malaysia, and Singapore is found at higher than or almost equal in frequency to G6PD Kaiping in those countries. Bioinformatics is needed to discover the genetic relationships between mutations that are common in Indonesia, and those found in China, India and the Middle East.…”

Optimizing a multiplex high resolution melting curve to diagnose G6PD deficiency based on viangchan and canton mutations

“…In addition, the molecular tests are also applied to detect Mediterranean mutation (563C>T), a common in the Southern Europe and Viangchan mutation (871G>A), the main kind in Lao and Cambodian widely (Joly, 2010). In China where has the close genetic interaction with Viet Nam, nine mutations (A95G, G392T, G487A, A493G, C592T, C1024T, C1360T, G1376T, G1388A) occupying more than 90% of G6PD deficient cases have been determined (Jiang et al, 2006;Yan et al, 2006). In these mutations, the Canton mutation (G1376T) and Kaiping mutation (G1388A)-two missense mutations in type 2 -occupying 53.8% have been successfully diagnosed by the HRM analysis (high resolution melting analysis) (Yan et al, 2010).…”