Premium
Genetic variants of tumor necrosis factor‐α (rs1800629) gene enhances susceptibility to malaria infection in West Africa
Author(s) -
Snyder Tara,
Noble Jenelle,
Funwei Roland,
Falade Catherine,
Ojurongbe Olusola,
Thomas Bolaji N
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.776.1
Subject(s) - biology , malaria , haplotype , genotype , allele , parasitemia , genetics , snp , gene , cerebral malaria , allele frequency , single nucleotide polymorphism , immunology , plasmodium falciparum
Malaria is still a disease that causes untold human death and suffering in many parts of the world. Despite the fact that the parasite genome has been sequenced, much remain to be deciphered, especially on factors that exacerbates or limit susceptibility to infection. We hypothesize that host genetics factors, with particular focus on genetic polymorphisms that affects gene transcription and variability in immune response, are major contributors to host susceptibility, resistance or disease severity. Therefore, we elucidated the genomic diversity and haplotype frequency of tumor nectrosis factor‐a (snp rs1800629) genes among and between malaria‐infected and control groups in West Africa, and extrapolated their role, if any, on parasitemia. To do this, genomic DNA samples obtained from 107 malaria‐infected (microscopy and PCR‐confirmed) patients and 380 uninfected controls from Nigeria, were subjected to a PCR‐RFLP analysis. We report that there is no significant difference in the genotypic ( p =0.15; 55.2% versus 50.0% for malaria‐infected and controls respectively) or allelic frequency ( p =0.21; 3.8% versus 8.4% for malaria‐infected and controls respectively) of the mutant variant of the vitamin D receptor (rs731236) gene. However, we found a statistically significant difference in the genotypic ( p =2.20E‐16) and allelic frequencies ( p =2.20E‐16) of the tumor nectrosis factor‐a (snp rs1800629) gene between malaria‐infected and control groups. The highest frequency of the mutant variant (77.6%) was found in the malaria‐infected group with the opposite reported among controls. In addition, haplotype frequencies were different between groups, with the most common haplotypes combining one form of the tumor nectrosis factor‐a mutant variant with a combination of the VDR mutant or wild type variant. Our observation clearly shows that tumor necrosis factor, as a proinflammatory cytokine, necessary to intitiate innate immune response is a major factor in susceptibility to malaria in West Africa. The preponderance of the mutant gene implies these patients cannot mount an effective immune response leaving parasitemia to increase uncontrolled until the initiation of adaptive immune response, thereby worsening disease. This, more than any other, may be the major factor delineating who is susceptible to disease or not, or the degree of infectivity and parasite load post‐infection. Future studies elucidating this genetic data in clearly delineated mild, uncomplicated versus severe disease groups viz a viz serum assays are ongoing. Support or Funding Information Funding provided by College of Health Sciences and Technology Faculty Development and Laboratory Support Fund, Rochester Institute of Technology