Genetic variants of beta-globin gene in Thai malaria patients.

Hemoglobin E (E26K variant of beta-globin gene) causing hemoglobinopathy is commonly observed in parts of Thailand, regardless of the hematologic disadvantage of the homozygotes. In order to detect further variants of the beta-globin gene, we performed variation screening for exon 1 of the beta-globin gene in 64 adult patients with P. falciparum malaria, living in northwest Thailand. We identified E26K and two novel variants, 59C>T and IVS+1G>T. IVS+1G>T lies on the splice donor site, and a substitution of A for G at the same site (IVS+1G>A) is known to be linked to beta-thalassemia. Thus, the biological significance of IVS+1G>T and its association with malarial infection should be clarified in future studies.

Lack of association between interleukin-10 gene promoter polymorphism, -1082G/A, and severe malaria in Thailand.

Interleukin-10 (IL-10) is an important cytokine in the down-regulation of inflammatory responses, and it has been reported that a low plasma concentration of IL-10 is associated with severe anemia and cerebral malaria in Plasmodium falciparum infections. The IL-10 gene is located on chromosome 1q31-32, and a promoter polymorphism (-1082G/A) is known to affect IL-10 protein production. In order to examine the possible association of the -1082G/A polymorphism with the severity of malaria, we studied 203 mild malaria, 164 non-cerebral severe malaria, and 109 cerebral malaria patients living in northwest Thailand. The genotyping was performed by a fluorescence resonance energy transfer (FRET) method. The frequencies of a major allele -1082A in mild malaria, in non-cerebral severe malaria, and in cerebral malaria patients were 92.6%, 92.1%, and 92.7% respectively. Our results showed no significant association of the -1082G/A polymorphism with the severity of malaria.

Polymorphisms of CD36 in Thai malaria patients.

The human protein CD36 is a major endothelial receptor for Plasmodium falciparum parasitized erythrocytes. Several polymorphisms causing CD36 deficiency have been identified to date: T1264G in Kenyan and Gambian patients, and C478T, 539delAC, and 1159insA in Japanese patients. The T1264G polymorphism is reportedly associated with protection from severe malaria in Kenyans, although there is a contradictory report suggesting the susceptibility of T1264G to severe malaria. The polymorphism of CD36 has not been thoroughly studied in Asian malaria patients. In this study, nucleotide sequence variations in exons 4, 5, 6, and 10 of CD36 were investigated in mild and cerebral malaria patients living in northwest Thailand. A novel synonymous substitution T1168C was detected in exon 10, whereas no variation was found in exons 4 and 6. The 539delAC allele in exon 5 was detected in Thai malaria patients, while T1264G, C478T, and 1159insA were not found. The 539delAC allele was observed in three cerebral malaria patients (3/107), but not in mild malaria patients (0/203). The frequency of 539delAC was significantly higher in cerebral malaria patients than in mild malaria patients (p = 0.040, Fisher's exact test). Although independent studies should be performed in order to confirm our findings, the 539delAC allele might be a high-risk variant for cerebral malaria in Thai.