Human genetic factors related to susceptibility to mild malaria in Gabon

Abstract

Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-␣ and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sicklecell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-␣ promoter mutations (at positions −238: 0.17 and −308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position −238 of the gene coding for the promoter region of TNF-␣ was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum. Genes and Immunity (2000) 1, 435-441.

Association of Haptoglobin Levels With Age, Parasite Density, and Haptoglobin Genotype in a Malaria-Endemic Area of Gabon

“…These genetic frequencies are consistent with other studies done in the same area. 18 Two hundred thirty-four children (45.8%) were slide negative for any species of Plasmodium. Of those who were positive, approximately half had greater than 100 parasites/L of blood.…”

“…Blood group was determined by serologic analysis and the sickle cell trait was detected by Hb electrophoresis. 18 The Hp genotype was determined by a polymerase chain reaction (PCR) using a method previously described with modifications. 19 The DNA was extracted from blood spots on filter paper using the QIAamp DNA Mini kit (Qiagen, Valencia, CA).…”

TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso

“…Using a case-control and cross-sectional design, they did not detect association of TNF polymorphisms with mild malaria or parasitemia. [13][14][15] In order to identify polymorphisms that might be associated with mild malaria and related phenotypes, we systematically screened the TNF gene in an urban population living in an endemic area in Burkina Faso.…”

Application of PCR Technologies to Humans, Animals, Plants and Pathogens from Central Africa

“…The most investigated polymorphism is located in the promoter region of NOS2, and concerns the point mutation NOS2 -954 G>C, which is associated with an increased production of NOS2. By the means of a PCR amplification followed by enzymatic digestion with BsaI, this point mutation was found in 18% of Gabonese individuals from the Banzabi ethnic group, mainly in the heterozygous state [22,25]. A similar high prevalence was found in another Gabonese population group, recruited in Lambaréné [34].…”

“…MBL is thought to be more effective at an early age, before effective acquired immune responses have developed, and low plasma concentrations of non-functional MBL have been attributed to mutations in the first exon of the MBL gene: MBL IVS-I-5 G>A, MBL 54 G>A and MBL 57 G>A. PCR-RFLP determination may be performed, using NlaIII (codon 52), BanI (codon 54) and MboII (codon 57) endonucleases. At least one MBP gene mutation was present in 34% of a Gabonese population sample (Banzabi), with an overall gene frequency of 0.03, 0.02 and 0.18 mutations at codons 52, 54 and 57, respectively [22,25]. There are other published MBL2 genotyping techniques, based on sequence-specific PCR, denaturing gradient gel electrophoresis of PCR-amplified fragments, real-time PCR with the hybridization of sequence-specific probes and sequence-based typing.…”