Association between IL1 gene polymorphism and human African trypanosomiasis in populations of sleeping sickness foci of southern Cameroon

<div><p>Background</p><p>Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to <i>Trypanosoma brucei</i> subspecies. In addition to the well-established environmental and behavioural risks of becoming infected, there is evidence for a genetic component to the response to trypanosome infection. We undertook a candidate gene case-control study to investigate genetic associations further.</p><p>Methodology</p><p>We genotyped one polymorphism in each of seven genes (<i>IL1A</i>, <i>IL1RN</i>, <i>IL4RN</i>, <i>IL6</i>, <i>HP</i>, <i>HPR</i>, and <i>HLA-G</i>) in 73 cases and 250 controls collected from 19 ethno-linguistic subgroups stratified into three major ethno-linguistic groups, 2 pooled ethno-linguistic groups and 11 ethno-linguistic subgroups from three Cameroonian HAT foci. The seven polymorphic loci tested consisted of three SNPs, three variable numbers of tandem repeat (VNTR) and one INDEL.</p><p>Results</p><p>We found that the genotype (TT) and minor allele (T) of <i>IL1A</i> gene as well as the genotype 1A3A of <i>IL1RN</i> were associated with an increased risk of getting <i>Trypanosoma brucei gambiense</i> and develop HAT when all data were analysed together and also when stratified by the three major ethno-linguistic groups, 2 pooled ethno-linguistic subgroups and 11 ethno-linguistic subgroups.</p><p>Conclusion</p><p>This study revealed that one SNP rs1800794 of <i>IL1A</i> and one VNTR rs2234663 of <i>IL1RN</i> were associated with the increased risk to be infected by <i>Trypanosoma brucei gambiense</i> and develop sleeping sickness in southern Cameroon. The minor allele T and the genotype TT of SNP rs1800794 in <i>IL1A</i> as well as the genotype 1A3A of <i>IL1RN</i> rs2234663 VNTR seem to increase the risk of getting <i>Trypanosoma brucei gambiense</i> infections and develop sleeping sickness in southern Cameroon.</p></div

Candidate genes and SNPs, VNTR and indel loci identified and selected for this study.

Candidate genes and SNPs, VNTR and indel loci identified and selected for this study.</p

Cochran-Mantel-Haenszel (CMH) association analysis results within the Cameroonian population.

Cochran-Mantel-Haenszel (CMH) association analysis results within the Cameroonian population.</p

Meta-analysis of the Fisher exact test results within the 11 ethno-linguistic groups clusters.

Meta-analysis of the Fisher exact test results within the 11 ethno-linguistic groups clusters.</p

Genotype frequency distribution for gene polymorphisms within the global Cameroon population.

Genotype frequency distribution for gene polymorphisms within the global Cameroon population.</p

Expected number and size of DNA fragments generated at each locus genotyped.

Expected number and size of DNA fragments generated at each locus genotyped.</p