Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage. G6PD deficiency is particularly prevalent in historically malaria-endemic areas. Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients. In this study, we systematically evaluated the prevalence of G6PD deficiency in the Kachin (Jingpo) ethnic group along the China-Myanmar border and determined the underlying G6PD genotypes. We surveyed G6PD deficiency in 1770 adult individuals (671 males and 1099 females) of the Kachin ethnicity using a G6PD fluorescent spot test. The overall prevalence of G6PD deficiency in the study population was 29.6% (523/1770), among which 27.9% and 30.6% were males and females, respectively. From these G6PD deficient samples, 198 unrelated individuals (147 females and 51 males) were selected for genotyping at 11 known G6PD single nucleotide polymorphisms (SNPs) in Southeast Asia (ten in exons and one in intron 11) using a multiplex SNaPshot assay. Mutations with known association to a deficient phenotype were detected in 43.9% (87/198) of cases, intronic and synonymous mutations were detected alone in 34.8% (69/198) cases and no mutation were found in 21.2% (42/198) cases. Five non-synonymous mutations, Mahidol 487G>A, Kaiping 1388G>A, Canton 1376G>T, Chinese 4 392G>T, and Viangchan 871G>A were detected. Of the 87 cases with known deficient mutations, the Mahidol variant was the most common (89.7%; 78/87), followed by the Kaiping (8.0%; 7/87) and the Viangchan (2.2%; 2/87) variants. The Canton and Chinese 4 variants were found in 1.1% of these 87 cases. Among them, two females carried the Mahidol/Viangchan and Mahidol/Kaiping double mutations, respectively. Interestingly, the silent SNPs 1311C>T and IVS11nt93T>C both occurred in the same 95 subjects with frequencies at 56.4% and 23.5% in tested females and males, respectively (P<0.05). It is noteworthy that 24 subjects carrying the Mahidol mutation and two carrying the Kaiping mutation also carried the 1311C>T/IVS11nt93T>C SNPs. Further studies are needed to determine the enzyme levels of the G6PD deficient people and presence of additional G6PD mutations in the study population.

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals

“…Although Mahidol and wild type variants do not differ in terms of K m for NADP + or glucose-6-phosphate and have similar catalytic efficiency, the thermo-stability of Mahidol variant is less than that of wild type G6PD enzyme and the folding properties of Mahidol protein are also impaired [21]. It has been reported that c.G487A substitution could reduce enzyme activity to 5–32% of wild-type activity which is consistent with our study results [28, 30]. G6PD Mahidol variant creates an Alu I restriction site (AGCT) which can be used to differentiate between wild type and G6PD Mahidol variant using PCR-RFLP method [31].…”

“…G6PD Mahidol is the most common deficient variant (occurs in 88–96% of G6PD-deficient subjects) in Thai-Myanmar border area [26–28]. This variant provides selective advantage against Plasmodium vivax but not against Plasmodium falciparum , which stipulates Plasmodium vivax has been the driving force for selective advantage conferred by Mahidol variant [29].…”

Prevalence and Molecular Study of G6PD Deficiency in the Dai and Jingpo Ethnic Groups in the Dehong Prefecture of the Yunnan Province

“…Our results indicate that the key pathogenic mutations of G6PD among the Dai and Jingpo groups of the Dehong prefecture were rs137852314 G>A, rs72554664 G>A, rs72554665 G>T, and rs137852341 G>T. The rs137852314 G>A and rs137852341 G>T mutations are frequently found across Southeast Asia, especially among the population of Myanmar [21] . Since the Dehong prefecture shares a border with Myanmar, frequent social exchanges between the local populations result in a genetic exchange.…”

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017

“…There were a total of 16 ethnic populations included in the current study, and the minorities were mainly distributed in the provinces of Hainan, Guangxi, and Zhejiang. Considering that the variant frequency is related to ethnic factors (Cai, Filosa, & Martini, ; Hu et al, ; Li et al, ; Yang et al, ), we analyzed the ethnic information of the 10,357 newborns. The G6PD pathogenic variants were then evaluated according to each ethnic group (Table ).…”