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Frequency of Interleukins IL1ß/IL18 and Inflammasome NLRP1/NLRP3 Polymorphisms in Sickle Cell Anemia Patients and their Association with Severity Score

[ Vol. 19 , Issue. 10 ]

Author(s):

Emerson de Almeida, Sonia Rejane Frantz, Purim Cesar, Andrea Monteiro Tarragô, Lilyane de Amorim Xabregas, Nadja Pinto Garcia, Allyson Guimarães Costa, Erich Vinicius de Paula and Adriana Malheiro*   Pages 776 - 783 ( 8 )

Abstract:


Background: Interleukins IL1ß/IL18 and Inflammasome NLRP1/NLRP3 polymorphisms can change the course of multiple human diseases, both inflammatory as infectious. SNPs these proteins were associated with the constructive activation of the Inflammasome and excessive production of IL-1β induce a serious autoinflammatory disease, as sickle cell anemia (SCA). The present study aims to association of interleukins IL1ß/IL18 and inflammasome NLRP1/NLRP3 polymorphisms in SCA patients in Amazon region and their association with severity score.

Methods: The study was developed at Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) with 21 patients diagnosed SCA (HbSS) and 50 Healthy Donor´s. Genetic polymorphisms (SNPs) in interleukins IL1ß/IL18 and inflammasome NLRP1/NLRP3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real time PCR. Simple and multiple logistic regression were performed to investigate association between the polymorphisms and the SCA and severe score.

Results: The genotypes C/C (IL18 -137G/C) and C/A (NLRP3, rs35829419) appear to be risk factors for SCA disease (IL18: G/G vs C/C OR=103.500 [95% CI: 8.32-1287.79, p<0.00001]; IL18: G/G vs G/C OR=7.360 [95% CI: 0.85-63.48, p=0.040]; IL18: G/G vs CC+CG OR=14.481 [95% CI: 1.79-117.32, p=0.002; NLRP3: C/C vs C/A: OR=10.967 [95% CI: 2.41-49.89, p=0.0004]). In addition, only allelic C (IL18 -137G/C) and A (NLRP3) appear to be risk factors for SCA disease (IL18: G vs C OR=6.366 [95% CI: 2.73-14.86, p<0.00001]; NLRP3: C vs A OR=8.383 [95% CI: 2.03-34.62, p=0.005]. No associations were observed between genotypes and alleles with the severity score.

Conclusion: Evidence of association between the IL18 (rs16944) and NLRP3 (rs35829419) polymorphisms with sickle cell anemia were described. Our results suggest that individuals with genotypes evaluated are associated SCA disease even though it does not influence the severe score.

Keywords:

SCA, Polymorphism, Proinflammatory cytokines, Inflammasome, interleukins.

Affiliation:

Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM



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