白细胞介素 IL1ß/IL18 和炎症小体 NLRP1/NLRP3 多态性在镰状细胞贫血患者中的频率及其与严重程度评分的关系。
Frequency of Interleukins IL1ß/IL18 and Inflammasome NLRP1/NLRP3 Polymorphisms in Sickle Cell Anemia Patients and their Association with Severity Score.
机构信息
Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, AM, Brazil.
Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Brazil.
出版信息
Curr Mol Med. 2019;19(10):776-783. doi: 10.2174/1566524019666190826143749.
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.
背景
白细胞介素 IL1ß/IL18 和炎性体 NLRP1/NLRP3 多态性可以改变多种人类疾病的进程，包括炎症性疾病和感染性疾病。这些蛋白质的 SNP 与炎性体的建设性激活和 IL-1β 的过度产生有关，导致严重的自身炎症性疾病，如镰状细胞贫血（SCA）。本研究旨在探讨亚马逊地区 SCA 患者中白细胞介素 IL1ß/IL18 和炎性体 NLRP1/NLRP3 多态性的相关性及其与严重程度评分的相关性。
方法
该研究在亚马逊血液基金会医院（HEMOAM）进行，共纳入 21 例 SCA（HbSS）患者和 50 名健康供体。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和实时 PCR 对白细胞介素 IL1ß/IL18 和炎性体 NLRP1/NLRP3 的遗传多态性（SNP）进行基因分型。采用简单和多元逻辑回归分析 SNP 与 SCA 和严重程度评分的相关性。
结果
IL18-137G/C 的 C/C 基因型和 NLRP3，rs35829419 的 C/A 基因型似乎是 SCA 疾病的危险因素（IL18：G/G 与 C/C 的比值比（OR）=103.500[95%可信区间（CI）：8.32-1287.79，p<0.00001]；IL18：G/G 与 G/C 的比值比（OR）=7.360[95%CI：0.85-63.48，p=0.040]；IL18：G/G 与 CC+CG 的比值比（OR）=14.481[95%CI：1.79-117.32，p=0.002]；NLRP3：C/C 与 C/A 的比值比（OR）=10.967[95%CI：2.41-49.89，p=0.0004]）。此外，只有等位基因 C（IL18-137G/C）和 A（NLRP3）似乎是 SCA 疾病的危险因素（IL18：G 与 C 的比值比（OR）=6.366[95%CI：2.73-14.86，p<0.00001]；NLRP3：C 与 A 的比值比（OR）=8.383[95%CI：2.03-34.62，p=0.005]）。未观察到基因型和等位基因与严重程度评分之间存在相关性。
结论
白细胞介素 IL18（rs16944）和 NLRP3（rs35829419）多态性与镰状细胞贫血相关的证据。我们的研究结果表明，评估的基因型与 SCA 疾病相关，尽管它不影响严重程度评分。
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