1. A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease.
- Author
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Tozatto-Maio K, Girot R, Ly ID, Rocha V, Silva Pinto AC, Diagne I, Benzerara Y, Dinardo CL, Kashima S, Leston-Araujo I, Kenzey C, Fonseca GHH, Rodrigues ES, Volt F, Jarduli LR, Ruggeri A, Mariaselvam CM, Gualandro SFM, Elayoubi H, Cunha R, Cappelli B, Malmegrim KCR, Simões BP, Gluckman E, and Tamouza R
- Subjects
- Adolescent, Adult, Africa epidemiology, Aged, Anemia, Sickle Cell epidemiology, Anemia, Sickle Cell immunology, Bacterial Infections epidemiology, Bacterial Infections immunology, Brazil epidemiology, Child, Child, Preschool, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Male, Middle Aged, Young Adult, Anemia, Sickle Cell genetics, Anemia, Sickle Cell microbiology, Bacterial Infections genetics, Toll-Like Receptor 2 genetics
- Abstract
Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34-0·75, P < 0·001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR = 3·18, 95% CI 1·53-6·61, P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2019
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