Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population

Abstract

Background The prevalence and genotypes of G6PD deficiency vary worldwide, with higher prevalence in malaria endemic areas. The first-time assessment of G6PD deficiency prevalence and molecular characterization of G6PD mutations in the Lao Theung population were performed in this study. Methods A total of 252 unrelated Lao Theung participants residing in the Lao People’s Democratic Republic (PDR) were recruited. All participant samples were tested for G6PD enzyme activity and G6PD gene mutations. The amplification refractory mutation system (ARMS)-PCR for detecting G6PD Aures was developed. Results The G6PD mutations were detected in 11.51% (29/252) of the participants. Eight G6PD mutations were detected. The G6PD Aures was the most common mutation identified in this cohort, which represented 58.62% (17/29) of all mutation. The mutation pattern was homogenous, predominantly involving the G6PD Aures mutation (6.75%), followed by 1.19% G6PD Union and 0.79% each G6PD Jammu, G6PD Mahidol and G6PD Kaiping. One subject (0.4%) each carried G6PD Viangchan and G6PD Canton. Interestingly, one case of coinheritance of G6PD Aures and Quing Yan was detected in this cohort. Based on levels of G6PD enzyme activity, the prevalence of G6PD deficiency in the Lao Theung population was 9.13% (23/252). The prevalence of G6PD deficient males and females (activity < 30%) in the Lao Theung population was 6.41% (5/78) and 1.72% (3/174), respectively, and the prevalence of G6PD intermediate (activity 30–70%) was 5.95% (15/252). Conclusions The G6PD Aures mutation is highly prevalent in the Lao Theung ethnic group. The common G6PD variants in continental Southeast Asian populations, G6PD Viangchan, Canton, Kaiping, Union and Mahidol, were not prevalent in this ethnic group. The technical simplicity of the developed ARMS-PCR will facilitate the final diagnosis of the G6PD Aures.

Massively parallel sequencing uncovered disease‐associated variant spectra of glucose‐6‐phosphate dehydrogenase deficiency, phenylketonuria and galactosemia in Vietnamese pregnant women

“…Due to the X-linked nature of this disease, males are not considered carriers. This study showed the prevalence of G6PD carriers to be 8.9% amongst Vietnamese pregnant women, close to the previously reported prevalence of roughly amongst the healthy populations in some Latin American and Southeast Asian countries (Matsuoka et al, 2004;Monteiro et al, 2014;Nuchprayoon et al, 2002;Phompradit et al, 2011;Sanephonasa et al, 2021). Of the five disease-associated G6PD variants detected amongst 290 unrelated variant-harbouring participants in this study, Viangchan/Jammu and Union are still the most frequently seen variants in Vietnam as well as other Southeast Asian populations with relatively high carrier frequencies the female population (Hue et al, 2009;Louicharoen & Nuchprayoon, 2005;Nuchprayoon et al, 2002;Ong et al, 2019;Phompradit et al, 2011;Satyagraha et al, 2015;Yusoff et al, 2003).…”

“…Of the five disease-associated G6PD variants detected amongst 290 unrelated variant-harbouring participants in this study, Viangchan/Jammu and Union are still the most frequently seen variants in Vietnam as well as other Southeast Asian populations with relatively high carrier frequencies the female population (Hue et al, 2009;Louicharoen & Nuchprayoon, 2005;Nuchprayoon et al, 2002;Ong et al, 2019;Phompradit et al, 2011;Satyagraha et al, 2015;Yusoff et al, 2003). Most importantly, apart from Viangchan/Jammu and Union variants, prevailing G6PD variants in Chinese, Thai, and other Southeast Asian populations were not found in this study (He et al, 2020;Liu et al, 2019;Louicharoen & Nuchprayoon, 2005;Matsuoka et al, 2004;Nuchprayoon et al, 2002;Ong et al, 2019;Phompradit et al, 2011;Sanephonasa et al, 2021;Satyagraha et al, 2015;Sulistyaningrum et al, 2020;Wang et al, 2008;Yusoff et al, 2003;Zhong et al, 2018). On the contrary, the remaining three pathogenic G6PD variants in this study, including Taiwan/Hakka, Anant and Sassari variants (which are very rarely observed in Southeast Asia and China), significantly add to the archive of previously reported Vietnamese G6PD disease-associated variants, including Vietnam 1, G7 > A (c.7G>A, p.Glu3Lys) and Vietnam 2, T10148 > G (c.117T>G, p.Phe66Cys) (Hue et al, 2009).…”

Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

“…In contrast, G6PD deficiency in Cambodia was almost exclusively caused by the Viangchan allele (Matsuoka et al 2005 ). Furthermore, specific subpopulations feature unique molecular G6PD patterns; for instance, the otherwise rare Aures allele constitutes the most common G6PD deficient variant in the Lao Theung population, the second largest ethnic group in Laos (Sanephonasa et al 2021 ).…”

Distribution of G6PD deficiency genotypes among Southeast Asian populations

“…Recently, an analysis of G6PD genotypes in the Lao Theung (or the Lao Mon-Khmer) population was reported from Laos [ 51 ]. This tribe is the second largest ethnic group, and their language (the Mon-Khmer language) is different from the Lao ethnic group, who speaks languages belonging to the Thai-Kra Dai family.…”

“…Next common are G6PD Union (3/29, 10.3%) and G6PD Jammu (2/29, 6.9%), but G6PD Vianghan was rare (1/29, 3.4%) among this tribe. All these results taken together strongly suggest that the Lao Theung tribe has different ancestral origins from the Lao ethnic group [ 51 ].…”