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

Li Q, Yang F, Liu R, Luo L, Yang Y, Zhang L, Liu H, Zhang W, Fan Z, Yang Z, Cui L, He Y - PLoS ONE (2015)

Bottom Line: Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients.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.The Canton and Chinese 4 variants were found in 1.1% of these 87 cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, Yunnan Province, China.

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.

No MeSH data available.


Related in: MedlinePlus

Representative electropherograms of the SNaPshot assay using multiplex extension primers.The homozygous alleles yield only one peak, whereas heterozygous alleles yield double peaks. Female A was heterozygous at both the Mahidol (487G/A) and the Viangchan (871G/A) loci. Female B was heterozygous at the Mahidol (487G/A) and Kaiping (1388G/A) loci.
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pone.0134593.g001: Representative electropherograms of the SNaPshot assay using multiplex extension primers.The homozygous alleles yield only one peak, whereas heterozygous alleles yield double peaks. Female A was heterozygous at both the Mahidol (487G/A) and the Viangchan (871G/A) loci. Female B was heterozygous at the Mahidol (487G/A) and Kaiping (1388G/A) loci.

Mentions: The female and male populations showed some distinctions in the prevalence and the presence of combined alleles. Whereas all five non-synonymous mutations were detected in the female population, only the two prevalent mutations (Mahidol and Kaiping) were detected in the male population (potentially due to the smaller sample size of the male population). The prevalence of the Mahidol mutation was not significantly different between males and females (P>0.05, Fisher’s exact test), being detected in 40.1% (59/147) tested females and 37.3% (19/51) males, respectively. The prevalence of the Kaiping variant was significantly different between tested males and females (P<0.001, Fisher’s exact test). In addition, one female was found to contain both Mahidol and Viangchan mutations, while another female harbored both Mahidol and Kaiping mutations (Fig 1, Table 2). Moreover, the two silent mutations were detected alone in 34.8% (69/198) of the cases, whereas 24 (12.1%) and 2 (1.0%) females with the two silent mutations were also found to carry the Mahidol and Kaiping mutations, respectively. In contrast, although the two silent mutations also occurred at a relatively high frequency of 23.5% in the male population, none was found to co-occur with either the Mahidol or the Kaiping mutation (Table 2).


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

Li Q, Yang F, Liu R, Luo L, Yang Y, Zhang L, Liu H, Zhang W, Fan Z, Yang Z, Cui L, He Y - PLoS ONE (2015)

Representative electropherograms of the SNaPshot assay using multiplex extension primers.The homozygous alleles yield only one peak, whereas heterozygous alleles yield double peaks. Female A was heterozygous at both the Mahidol (487G/A) and the Viangchan (871G/A) loci. Female B was heterozygous at the Mahidol (487G/A) and Kaiping (1388G/A) loci.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520570&req=5

pone.0134593.g001: Representative electropherograms of the SNaPshot assay using multiplex extension primers.The homozygous alleles yield only one peak, whereas heterozygous alleles yield double peaks. Female A was heterozygous at both the Mahidol (487G/A) and the Viangchan (871G/A) loci. Female B was heterozygous at the Mahidol (487G/A) and Kaiping (1388G/A) loci.
Mentions: The female and male populations showed some distinctions in the prevalence and the presence of combined alleles. Whereas all five non-synonymous mutations were detected in the female population, only the two prevalent mutations (Mahidol and Kaiping) were detected in the male population (potentially due to the smaller sample size of the male population). The prevalence of the Mahidol mutation was not significantly different between males and females (P>0.05, Fisher’s exact test), being detected in 40.1% (59/147) tested females and 37.3% (19/51) males, respectively. The prevalence of the Kaiping variant was significantly different between tested males and females (P<0.001, Fisher’s exact test). In addition, one female was found to contain both Mahidol and Viangchan mutations, while another female harbored both Mahidol and Kaiping mutations (Fig 1, Table 2). Moreover, the two silent mutations were detected alone in 34.8% (69/198) of the cases, whereas 24 (12.1%) and 2 (1.0%) females with the two silent mutations were also found to carry the Mahidol and Kaiping mutations, respectively. In contrast, although the two silent mutations also occurred at a relatively high frequency of 23.5% in the male population, none was found to co-occur with either the Mahidol or the Kaiping mutation (Table 2).

Bottom Line: Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients.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.The Canton and Chinese 4 variants were found in 1.1% of these 87 cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, Yunnan Province, China.

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.

No MeSH data available.


Related in: MedlinePlus