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1.
Hum Genet ; 139(6-7): 833, 2020 06.
Article in English | MEDLINE | ID: mdl-32445039

ABSTRACT

In the original article publication, the affiliation of the author Ana Coutinho is incorrect.

2.
Hum Genet ; 139(6-7): 821-831, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32277285

ABSTRACT

Schistosomes induce severe hepatic disease, which is fatal in 2-10% of cases, mortality being higher in cases of co-infection with HBV or HCV. Hepatic disease occurs as a consequence of the chronic inflammation caused by schistosome eggs trapped in liver sinusoids. In certain individuals, the repair process leads to a massive accumulation of fibrosis in the periportal spaces. We and others have shown that genetic variants play a crucial role in disease progression from mild to severe fibrosis and explain why hepatic fibrosis progresses rapidly in certain subjects only. We will review here published findings concerning the strategies that have been used in the analysis of hepatic fibrosis in schistosome-infected individuals, the genetic variants that have associated with fibrosis, and variants in new pathways crucial for fibrosis progression. Together, these studies show that the development of fibrosis is under the tight genetic control of various common variants with moderate effects. This polygenic control has made it possible to develop models that identify schistosome-infected individual at risk of severe hepatic disease. We discuss the performances and limitations of these models.


Subject(s)
Algorithms , Genetic Markers , Liver Diseases, Parasitic/diagnosis , Precision Medicine , Schistosoma/genetics , Schistosomiasis/complications , Severity of Illness Index , Animals , Disease Progression , Humans , Liver Diseases, Parasitic/etiology , Liver Diseases, Parasitic/genetics , Schistosoma/immunology , Schistosoma/pathogenicity , Schistosomiasis/immunology , Schistosomiasis/parasitology
3.
Int J Immunogenet ; 47(4): 351-358, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32065450

ABSTRACT

Single nucleotide polymorphisms (SNPs) in immune-related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue-related symptoms (aged 1-15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV-infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98-3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07-3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08-0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN-λ expression and DENV immunopathogenesis.


Subject(s)
Dengue Virus/genetics , Dengue/genetics , Interferons/genetics , Adolescent , Alleles , Child , Child, Preschool , Dengue/immunology , Dengue/pathology , Dengue/virology , Dengue Virus/immunology , Dengue Virus/pathogenicity , Female , Genotype , Humans , Infant , Male , Polymorphism, Single Nucleotide/genetics , Severity of Illness Index
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