title: Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia.
abstract: Sickle cell anemia (SCA), a disorder characterized by both acute and chronic inflammation, exhibits substantial phenotypic variability. Interleukin-1 beta (IL-1β) and IL-6 are important in acute and chronic diseases, and their single nucleotide polymorphisms (SNPs) have been considered as predictors of prognosis in several inflammatory conditions. This study aims at exploring possible association of IL-1β and IL-6 SNPs as potential genetic modifiers and or predictors of SCA clinical and laboratory phenotypes. This cross-sectional study involved 107 SCA patients and 110 age, sex and ethnicity-matched healthy individuals. The SNPs were identified by PCR-RFLP for IL-1β (-511C>T and +3954C>T) and IL-6 (-597G>A and -174G>C) genes. Associations between these SNPs and the clinical and laboratory profiles of patients with SCA were then determined. Allelic and genotypic frequencies of IL-1β and IL-6 SNPs between patients with SCA and controls were similar and followed HWE. IL-1β +3954C>T SNP was associated with increased risk of osteonecrosis, elevated pulmonary arterial pressure and lower absolute reticulocyte count, while IL-6 -597G>A was associated with higher likelihood of retinopathy and leg ulcer. These data indicate that IL-1β and IL-6 gene SNPs are associated with SCA complications among Brazilian patients and may act as genetic predictors of SCA clinical heterogeneity.
authors.affiliation: Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina/UNIFESP, São Paulo, Brazil.
authors.forename: Perla
authors.initials: P
authors.lastname: Vicari
authors.affiliation: Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina/UNIFESP, São Paulo, Brazil.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Adegoke
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Diego Robles
authors.initials: DR
authors.lastname: Mazzotti
authors.affiliation: Disciplina de Hematologia e Oncologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil.
authors.forename: Rodolfo Delfini
authors.initials: RD
authors.lastname: Cançado
authors.affiliation: Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina/UNIFESP, São Paulo, Brazil.
authors.forename: Maria Aparecida Eiko
authors.initials: MA
authors.lastname: Nogutti
authors.affiliation: Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina/UNIFESP, São Paulo, Brazil. Electronic address: stella.figueiredo@unifesp.br.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Figueiredo
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6
keywords: Genetic polymorphism; Inflammation; Interleukins; Prognosis; Sickle cell anemia