Résumé
Background: Urogenital schistosomiasis from Schistosoma haematobium and mesenteric schistosomiasis from S. mansoni are major parasitic diseases in Africa. While the role of the human genetic background in the control of infection intensity is clearly established for S. mansoni, this is not the case for S. haematobium. TNF-α is a strong pro-inflammatory cytokine that favours granuloma formation, causing immunological pathologies in schistosomiasis. The overexpression of TNF-α and functional variants located in the TNF-α promoter are implicated in many diseases and clinical parameters.Objectives: This study investigated the association between genetic variants of the TNF-α promoter and urogenital schistosomiasis morbidity in Benin.Methods:We examined 334 urine samples from young Beninese men and assayed urinary Eosinophil Cationic Protein (ECP), a marker of bladder inflammation. Abdominal-pelvic ultrasound was performed in a sub-group of 146 men to assess morbidity. From blood, ELISA quantification and TNF-α promoter sequencing was performed to analyse the association between genetic variants and morbidity.Results:The results showed that 25.4% were infected with significantly higher average TNFα (U=5888; P=0.0098) and ECP (U=912,5; P <0.0001;) levels in infected patients compared to uninfected patients. A positive correlation was observed between egg count and both TNF-α and ECP levels. The morbidity observed were bladder irregularity, bladder thickening, and dilatation of the kidneys and ureters. We found that the G mutant allele of the rs3093660 locus at position -133 on the TNF-α promoter was significantly associated with the morbidity, and patients with the GG genotype exhibited 4 times more severe forms of the disease than mild forms (X 2 =4.5; P= 0.03). Furthermore, patients with the GG genotype at this locus had a significantly higher ECP rate compared to patients with the CC genotype. (W=75; P= 0.039).Conclusion:Our results suggest for the first time allele G mutant in the locus rs3093660 as a risk factor for severe urogenital schistosomiasis.