Association Between Absolute Neutrophil Count and Variation at <i>TCIRG1</i>: The NHLBI Exome Sequencing Project

Rosenthal, Elisabeth; Makaryan, Vahagn; Burt, Amber; Crosslin, David R.; Kim, Daniel S.; Smith, Joshua D.; Nickerson, Deborah A.; Reiner, Alex P.; Rich, Stephen S.; Jackson, Rebecca D.; Ganesh, Santhi K.; Polfus, Linda M.; Qi, Lihong; Dale, David C.; Jarvik, Gail P.

doi:10.1002/gepi.21976

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…It is interesting to note that TCIRG1 showed a greater than 20% up-regulation in blood of AD, blood of MCI and brain of AD. Mutations in this gene can cause lower absolute neutrophil count and may be responsible for infantile malignant osteopetrosis (IMO) disease 35 , 36 . However, its role in AD or dementia is not yet proven, and it may be related to neutrophil function and immunity.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis and Biomarker Study for Alzheimer’s Disease

Wang

Long

et al. 2018

Sci Rep

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Revealing the relationship between dysfunctional genes in blood and brain tissues from patients with Alzheimer’s Disease (AD) will help us to understand the pathology of this disease. In this study, we conducted the first such large systematic analysis to identify differentially expressed genes (DEGs) in blood samples from 245 AD cases, 143 mild cognitive impairment (MCI) cases, and 182 healthy control subjects, and then compare these with DEGs in brain samples. We evaluated our findings using two independent AD blood datasets and performed a gene-based genome-wide association study to identify potential novel risk genes. We identified 789 and 998 DEGs common to both blood and brain of AD and MCI subjects respectively, over 77% of which had the same regulation directions across tissues and disease status, including the known ABCA7, and the novel TYK2 and TCIRG1. A machine learning classification model containing NDUFA1, MRPL51, and RPL36AL, implicating mitochondrial and ribosomal function, was discovered which discriminated between AD patients and controls with 85.9% of area under the curve and 78.1% accuracy (sensitivity = 77.6%, specificity = 78.9%). Moreover, our findings strongly suggest that mitochondrial dysfunction, NF-κB signalling and iNOS signalling are important dysregulated pathways in AD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Systematic Analysis and Biomarker Study for Alzheimer’s Disease

Wang

Long

et al. 2018

Sci Rep

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“…Clearly, some familial NPs might be due to other mutations that causes low ANC; see Table for some examples, mostly in non‐African populations. The list of candidate genes produced by 1000 Genomes Project genome‐wide association study (GWAS) (e.g., CDK6, PSMD3, ARPC2, HLA‐B , and CSF3) as well as TCIRG1 variations might be of interest for future research.…”

Section: Enp and The Duffy‐null Traitmentioning

confidence: 99%

Ethnic benign neutropenia: A phenomenon finds an explanation

Palmblad

Höglund

2018

Pediatric Blood & Cancer

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Ethnic benign neutropenia (ENP) is the most common form of neutropenia (NP) worldwide, if an absolute blood neutrophil count (ANC) of < 1.5 G/L is used as definition. In 2009, ENP was associated with a gene variation in the ACKR1/DARC gene, the same variation that also confers the Duffy-null trait. In 2017, a novel mechanism for ENP was introduced, questioning if ENP is a true neutropenic state, when the body's total neutrophil count (TBNC) is concerned. Here, we summarize the current knowledge of ENP, asking (1) How well does the peripheral blood ANC predict the TBNC? (2) Can we improve methods for assessing TBNC? (3) Will estimates of TBNC predict infection propensity and reduce the need for further, costly workup?

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“…According to the definition of neutrophilia (i.e., absolute neutrophil count >7700 cells/μL),22 approximately 11% of the patients had neutrophilia, with a mean of 8510±89 cells/μL.…”

Section: Resultsmentioning

confidence: 99%

<p>Assessment of T helper 17-associated cytokines in thromboangiitis obliterans</p>

Keramat¹,

Sadeghian²,

Keramati³

et al. 2019

JIR

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BackgroundThe management of thromboangiitis obliterans (TAO) remains a medical challenge because of its unknown etiology. It is also not known whether it is a systemic or localized disease or a type of autoimmune vasculitis.MethodsIn this study, we evaluated the serum level of IL-17 and IL-23 which increase in both systemic inflammation and autoimmunity, in 60 TAO patients and 30 age- and smoking habit-matched controls. Also, IL-22, which has reported high level during infection but not in autoimmunity, was evaluated.ResultsThe serum levels of IL-17, IL-22 and IL-23 were significantly higher in the TAO patients in comparison with the controls (P<0.001). Notably, the serum levels of IL-17, IL-22 and IL-23 were highest in the patients with the chief complaint of chronic ulcer and lowest in the patients with gangrene (P<0.05). Also, the serum level of IL-22 was significantly higher in the anemic patients in comparison with the non-anemic patients (P=0.03).ConclusionOwing to our findings, TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. Also, according to our findings regarding the high level of IL-22, the trigger of TAO development may be an infectious pathogen. However, additional research is highly recommended to investigate whether TAO is an infectious disease or an infectious-induced autoimmunity.

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Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project

Cited by 11 publications

References 29 publications

Systematic Analysis and Biomarker Study for Alzheimer’s Disease

Systematic Analysis and Biomarker Study for Alzheimer’s Disease

Ethnic benign neutropenia: A phenomenon finds an explanation

<p>Assessment of T helper 17-associated cytokines in thromboangiitis obliterans</p>

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