Generic placeholder image

Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

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

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*

Volume 19, Issue 10, 2019

Page: [776 - 783] Pages: 8

DOI: 10.2174/1566524019666190826143749

Price: $65


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.

Frenette PS, Atweh GF. Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest 2007; 117(4): 850-8.
[] [PMID: 17404610]
Solomou E, Kraniotis P, Kourakli A, Petsas T. Extent of silent cerebral infarcts in adult sickle-cell disease patients on magnetic resonance imaging: is there a correlation with the clinical severity of disease? Hematol Rep 2013; 5(1): 8-12.
[] [PMID: 23888239]
van den Tweel XW, van der Lee JH, Heijboer H, Peters M, Fijnvandraat K. Development and validation of a pediatric severity index for sickle cell patients. Am J Hematol 2010; 85(10): 746-51.
[] [PMID: 20806231]
Pearson SR, Alkon A, Treadwell M, Wolff B, Quirolo K, Boyce WT. Autonomic reactivity and clinical severity in children with sickle cell disease. Clin Auton Res 2005; 15(6): 400-7.
[] [PMID: 16362543]
Dutra FF, Bozza MT. Heme on innate immunity and inflammation. Front Pharmacol 2014; 5: 115.
[] [PMID: 24904418]
Bayley J-P, Ottenhoff THM, Verweij CL. Is there a future for TNF promoter polymorphisms? Genes Immun 2004; 5(5): 315-29.
[] [PMID: 14973548]
Sortica VA, Cunha MG, Ohnishi MD, et al. IL1B, IL4R, IL12RB1 and TNF gene polymorphisms are associated with Plasmodium vivax malaria in Brazil. Malar J 2012; 11: 409.
[] [PMID: 23217179]
Kumar D, Tiwary P, Chakravarty J, Sundar S. Association of interleukin-18 gene polymorphism with susceptibility to visceral leishmaniasis in endemic area of Bihar, an Indian Population Sci World J 2014; 2014.
Folwaczny M, Glas J, Török H-P, et al. Polymorphisms of the interleukin-18 gene in periodontitis patients. J Clin Periodontol 2005; 32(5): 530-4.
[] [PMID: 15842270]
Sebastiani P, Nolan VG, Baldwin CT, et al. A network model to predict the risk of death in sickle cell disease. Blood 2007; 110(7): 2727-35.
[] [PMID: 17600133]
Ferreira S da C, Chachá SGF, Souza FF, et al. IL-18, TNF, and IFN-γ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury. J Med Virol 2015; 87(10): 1689-96.
[] [PMID: 25952099]
El-Omar EM, Carrington M, Chow W-H, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000; 404(6776): 398-402.
[] [PMID: 10746728]
Bhat IA, Naykoo NA, Qasim I, et al. Association of interleukin 1 beta (IL-1β) polymorphism with mRNA expression and risk of non small cell lung cancer. Meta Gene 2014; 2: 123-33.
[] [PMID: 25606396]
Jin Y, Mailloux CM, Gowan K, et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007; 356(12): 1216-25.
[] [PMID: 17377159]
Davis BK, Wen H, Ting JP-Y. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol 2011; 29: 707-35.
[] [PMID: 21219188]
Belcher JD, Chen C, Nguyen J, et al. Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 2014; 123(3): 377-90.
[] [PMID: 24277079]
Verma D, Lerm M, Blomgran Julinder R, Eriksson P, Söderkvist P, Särndahl E. Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: relation to common inflammatory diseases? Arthritis Rheum 2008; 58(3): 888-94.
[] [PMID: 18311798]
Chi DZ, Chen J, Huang DP. Influence of interleukin-1β and interleukin-6 gene polymorphisms on the development of acute pancreatitis. Genet Mol Res 2015; 14(1): 975-80.
[] [PMID: 25730036]
Santos KN, Almeida MK, Fecury AA, Costa CA, Martins LC. Analysis of Polymorphisms in the Interleukin 18 Gene Promotor (-137 G/C and -607 C/A) in Patients Infected with Hepatitis C Virus from the Brazilian Amazon. Arq Gastroenterol 2015; 52(3): 222-7.
[] [PMID: 26486291]
Karra VK, Gumma PK, Chowdhury SJ, et al. IL-18 polymorphisms in hepatitis B virus related liver disease. Cytokine 2015; 73(2): 277-82.
[] [PMID: 25802197]
de Zoete MR, Palm NW, Zhu S, Flavell RA. Inflammasomes. Cold Spring Harb Perspect Biol 2014; 6(12): a016287-7.
[] [PMID: 25324215]
Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S, Jin Y, et al. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. Proc Natl Acad Sci U S A National Academy of Sciences 2013; 110: 2952-6.
Pontillo A, Oshiro TM, Girardelli M, Kamada AJ, Crovella S, Duarte AJS. Polymorphisms in inflammasome’ genes and susceptibility to HIV-1 infection. J Acquir Immune Defic Syndr 2012; 59(2): 121-5.
[] [PMID: 22227487]
Hitomi Y, Ebisawa M, Tomikawa M, et al. Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma. J Allergy Clin Immunol 2009; 124(4): 779-85.e6.
[] [PMID: 19767079]
Pontillo A, Brandão LA, Guimarães RL, Segat L, Athanasakis E, Crovella SA. 3'UTR SNP in NLRP3 gene is associated with susceptibility to HIV-1 infection. J Acquir Immune Defic Syndr 2010; 54(3): 236-40.
[] [PMID: 20502346]
Verma D, Särndahl E, Andersson H, et al. The Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to excessive interleukin-1β and IL-18 production. PLoS One 2012; 7(4)e34977
[] [PMID: 22529966]
Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 2001; 29(3): 301-5.
[] [PMID: 11687797]
Zhang Q, Fan HW, Zhang JZ, Wang YM, Xing HJ. NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans. Genet Mol Res 2015; 14(4): 13968-80.
[] [PMID: 26535712]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy