Mutations and haplotype analysis of the G6PD locus in the Southeast Asia population

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the common hereditary enzymopathy in Southeast Asian caused by mutation of G6PD. G6PD Viangchan (871G vector A) is the most common mutation in Southeast Asian. We studied G6PD mutations and polymorphisms in Southeast Asian to clarify the genetic relationship between them. Cord blood samples from 172 normal neonates and 195 jaundiced newborns at Buriram Hospital, 303 jaundiced newborns at King Chulalongkorn Memorial Hospital and peripheral blood samples from 195 migrant Cambodian,Laotian, and Myanmars laborers at Chunthaburi and 78 migrant Myanmars laborers admitted to the Samutsakhon Hospital were assayed for G6PD activity. The prevalence of G6PD deficiency was high in Cambodians (17 of 92 males; 18.5%), Thais (3 of 14 males) and Laotians (12 of 69 males; 17.4%) but was less in Myanmars (7 of 72 males; 9.7%). Among the jaundiced newborns, the prevalence of G6PD deficiency was very high in Cambodians (14 of 56 males; 25.0%), Thai (30 of 188 males; 16.0%) and Laotian (8 of 39 males; 20.5%). PCR-RFLP method was used to identify G6PD mutations in G6PD deficient samples and do haplotype analysis of the G6PD locus. G6PD Viangchan (871G>A) was the most common mutation among Cambodian (28 of 34; 82.4%), Thai (21 of 44; 47.7%) and Laotian (12 of 26; 46.2%) but not Myanmars (0 of 8) G6PD deficiency. G6PD Mahidol was the prevalent mutation in Myanmars (5 of 8; 62.5%), Thai (2 of 44; 4.5%) but not found in Cambodian or Laotian. The haplotype of G6PD Viangchan had 2 forms consisted of -,-,+,+,+,+ (Pvu II: 611C vector G, Sca I: 175C vector T, BspH I: 163C vector T, Pst I: 1116G vector A, Bcl I: 1311C vector T, Nla III: 93T vector C) (46 of 49; 93.9%), which similar to 21.3% (N = 202) (p < 0.0001) of G6PD normal and another form is -,-,+,+,+,-(3 of 49; 6.1%). G6PD Viangchan associates with 1311T and 93C significantly. While haplotype of other G6PD mutations and 69.8% of normal was -,-,+,+,-,-. G6PD Viangchan is themost common G6PD deficient mutation among Cambodian, Thai and Laotian with allele frequency of 0.10, 0.06 and 0.06 respectively. The 1311T allele is the ancestral polymorphism of G6PD Viangchan.