PREVALENCE OF N-TERMINAL MUTATION OF PYRUVATE KINASEAMONG VULNERLABLE MALARIA-RISK POPULATION IN SOUTHEAST ASIA

Abstract

Pyruvate kinase (PK) is an important enzyme in glycolysis pathway, which has function in producing ATP for cellular activities. Mutation of PKLR gene causes a hematological disorder, known as PK deficiency (PKD). It has been observed that hemolytic disorder is the key to protect against malaria infection and to reduce the severity of malaria. Recently, a novel mutation at N-terminus of PK has been found in Southeast Asian population. This mutation results in a change of amino acid residue 41 from arginine (R) to glutamine (Q) and is designated as PKLRR41Q. However, the prevalence and association between PKLRR41Q and malaria in human is not known. The results from 267 malaria patients showed that the prevalence of PKLRR41Q was 4.87% with allele frequency was 0.026. The association study demonstrated that the number of parasite attacks was significantly higher in patients with PKLRR41Q than in patients without PKLRR41Q (p=0.001). The allele frequency of PKLRR41Q with hyperparasitemia (P. falciparum: 0.100 and P. vivax: 0.104) was higher than none hyperparasitemia (P. falciparum: 0.051 and P. vivax: 0.023). Odds of hyperparasitemia was higher in patients with PKLRR41Q than in patients without PKLRR41Q (P. falciparum; OR: 2.18, 95% CI: 0.340 - 14.096, p= 0.410, P. vivax; OR: 4.20, 95% CI: 0.709 - 24.880, p= 0.114). Moreover, the reticulocyte count in patients with PKLRR41Q was increased, compared to that of patients without PKLRR41Q (p=0.700). It is speculated that increasing of reticulocyte in patients with PKLRR41Q could be due to hemolysis from infection and PKD and could contribute to proliferation of parasites. These findings suggest that PKLRR41Q is a common PKLR mutation in Southeast Asian population. The presence of PKLRR41Q may increase a tendency of number of parasite attacks and hyperparasitemia.