<i>IL1A</i>
            rs1800587 Associates with Chronic Noncrisis Pain in Sickle Cell Disease

Hu, Xiaoyu; Jhun, Ellie H.; Yao, Yingwei; Molokie, Robert E.; Wilkie, Diana J.; Wang, Zaijie J.

doi:10.2217/pgs-2016-0085

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…The severity and symptoms of sickle cell anemia (SCA) and the other SCD genotypes are surprisingly variable [234], and genetic modulation of the production of cytokines, other inflammatory molecules, and their receptors may constitute one of the mechanisms that contribute to this variation. Polymorphisms in the genes encoding IFNγ and TNF-α have been shown to present associations with infectious complications and stroke [235–237], while several genes in the TGF-beta/BMP signaling pathway have been associated with the incidence of leg ulcers [238], and the IL1A rs1800587 SNP may influence chronic pain in SCD [239].…”

Section: Chronic Inflammatory Mechanisms In Sickle Cell Diseasementioning

confidence: 99%

Inflammation in sickle cell disease

2018

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The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.

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Section: Chronic Inflammatory Mechanisms In Sickle Cell Diseasementioning

confidence: 99%

Inflammation in sickle cell disease

2018

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“…Co-inheritance of α-thalassaemia has been inconsistently associated to variable levels of VOC (Platt et al , 1991; Darbari et al , 2012; Tarer et al , 2006). In addition, a few observational studies have explored the associations of VOC with targeted variants in genes coding for enzymes that metabolize analgesics or inflammation-related proteins, with encouraging results (Hu et al , 2016; Jhun et al , 2015; Mendonça et al , 2010; Belfer et al , 2014; Galarneau et al , 2013). Specifically, one study identified and prioritised a total of 115 single nucleotide polymorphisms (SNPs) in 49 candidate genes that modified pain among African-American SCD patients (Jhun et al , 2015); but this has not been followed by genotype to phenotype investigations.…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic factors are associated with pain and hospitalisation rates in sickle cell anaemia in Cameroon

et al. 2017

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We aimed to investigate the clinical and genetic predictors of painful vaso-occlusive crises (VOC) in sickle cell disease (SCD) in Cameroon. Socio-demographics, clinical variables/events and haematological indices were acquired. Genotyping was performed for 40 variants in 17 pain-related genes, three fetal haemoglobin (HbF)-promoting loci, two kidney dysfunctions-related genes, and HBA1/HBA2 genes. Statistical models using regression frameworks were performed in R . A total of 436 hydoxycarbamide- and opioid-naïve patients were studied; median age was 16 years. Female sex, body mass index, Hb/HbF, blood transfusions, leucocytosis and consultation or hospitalisation rates significantly correlated with VOC. Three pain-related genes variants correlated with VOC (CACNA2D3-rs6777055, P = 0·025; DRD2-rs4274224, P = 0·037; KCNS1-rs734784, P = 0·01). Five pain-related genes variants correlated with hospitalisation/consultation rates. (COMT-rs6269, P = 0·027; FAAH-rs4141964, P = 0·003; OPRM1-rs1799971, P = 0·031; ADRB2-rs1042713; P < 0·001; UGT2B7-rs7438135, P = 0·037). The 3·7 kb HBA1/HBA2 deletion correlated with increased VOC (P = 0·002). HbF-promoting loci variants correlated with decreased hospitalisation (BCL11A-rs4671393, P = 0·026; HBS1L-MYB-rs28384513, P = 0·01). APOL1 G1/G2 correlated with increased hospitalisation (P = 0·048). This first study from Africa has provided evidence supporting possible development of genetic risk model for pain in SCD.

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“…The SNP IL1A −889C/T has also been associated with several inflammatory diseases, such as allergic rhinitis, sepsis, periodontitis, and chronic pain in sickle cell anemia . In addition, the presence of the T allele has been linked with increased IL‐1α production .…”

Section: Discussionmentioning

confidence: 99%

Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

Salum

Castro

Moreira

et al. 2019

American J Industrial Med

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Introduction: Silicosis is a fibrotic lung disease resulting from the inhalation of crystalline silica and can be classified as simple or complicated according to the International Labour Organization criteria. Furthermore, individuals exposed to crystalline silica also have a higher risk for the development of tuberculosis (Tb).The contribution of inflammatory cytokines to the risk of silicosis and Tb in different populations has previously been reported. Since genetic background might be related to susceptibility to silicosis and Tb, the study of polymorphisms within IL-1α, IL-1β, and tumor necrosis factor protein-coding genes may contribute to elucidating the genetic basis of these diseases.Methods: Single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction using restriction fragment length polymorphism or by Taqman methodology, in a sample of 102 silica-exposed patients from Brazil.Results: No significant associations were observed between the SNPs studied and the severity of silicosis. However, significant associations were found between Tb and the C allele (odds ratio [OR] = 1.93, 95% confidence interval [CI], 1.01-3.73) and the CC genotype (OR = 2.34, 95% CI, 1.04-5.31) of IL1A −899C>T. The IL1B +3954C>T polymorphism also showed an association with Tb (T allele dominant model OR = 2.38, 95% CI, 1.04-5.41). Conclusion:These preliminary results demonstrate that the IL1A and IL1B gene variations may contribute to some extent to susceptibility to Tb, but not silicosis.However, additional studies are still needed to confirm these results.

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IL1A rs1800587 Associates with Chronic Noncrisis Pain in Sickle Cell Disease

Cited by 9 publications

References 44 publications

Inflammation in sickle cell disease

Inflammation in sickle cell disease

Clinical and genetic factors are associated with pain and hospitalisation rates in sickle cell anaemia in Cameroon

Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

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