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An ADAM10 promoter polymorphism is a functional variant in severe sepsis patients and confers susceptibility to the development of sepsis

Overview of attention for article published in Critical Care, December 2015
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  • Above-average Attention Score compared to outputs of the same age (52nd percentile)

Mentioned by

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6 X users

Citations

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34 Dimensions

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38 Mendeley
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Title
An ADAM10 promoter polymorphism is a functional variant in severe sepsis patients and confers susceptibility to the development of sepsis
Published in
Critical Care, December 2015
DOI 10.1186/s13054-015-0796-x
Pubmed ID
Authors

Lili Cui, Yan Gao, Yuliu Xie, Yan Wang, Yujie Cai, Xin Shao, Xiaotang Ma, You LI, Guoda Ma, Gen Liu, Wanwen Cheng, Yu Liu, Tingting Liu, Qunwen Pan, Hua Tao, Zhou Liu, Bin Zhao, Yiming Shao, Keshen Li

Abstract

Although genetic variants of the A disintegrin and metalloproteinase 10 (ADAM10) gene have been shown to be associated with susceptibility to several inflammatory-related diseases, to date little is known about the clinical relationship in the development of sepsis. Two genetic variants in the promoter of ADAM10 were selected to analyze the potential association with the risk of sepsis. A total of 440 sepsis patients and 450 matched healthy individuals in two independent Chinese Han population were enrolled. Pyrosequencing and polymerase chain reaction-length polymorphism was used to determine the genotypes of the rs514049 and rs653765. A real-time qPCR method was used to detect the mRNA level of ADAM10. Enzyme-linked immunosorbent assay was used to measure the expression levels of substrates CX3CL1, interleukin (IL)-6R, tumor necrosis factor alpha (TNF-α), and the pro-inflammatory cytokines IL-1β and IL-6. Luciferase assay was used to analyze the activities of the promoter haplotypes of ADAM10. No statistically significant differences between sepsis cases and controls in the genotype or allele frequencies were observed, suggesting that ADAM10 single nucleotide polymorphisms (SNPs) may not be risk factors for the occurrence of sepsis. A significant difference in the genotype and allele frequencies of the rs653765 SNP between patients with sepsis subtype and severe sepsis (P = 0.0014) or severe sepsis/sepsis shock (P = 0.0037) were observed. Moreover, the rs653765 CC genotype in severe sepsis showed a higher ADAM10 level compared to healthy groups, and the rs653765 CC polymorphism had a strong impact on the production of the ADAM10 substrates CX3CL1, IL-6R and TNF-α. Furthermore, the functional assay showed that ADAM10 C-A haplotype carriers exhibited significantly higher reporter activity compared with the T-A carriers and T-C carriers in human acute monocytic leukemia cell line. Our data initially indicated the ADAM10 rs653765 polymorphism was associated with the development of severe sepsis; the risk CC genotype could functionally affect the expression level of ADAM10 mRNA and was accompanied by the up-regulation of its substrates. Thus, ADAM10 might be clinically important and play a critical role in the pathogenesis of the development of sepsis, with potentially important therapeutic implications.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Colombia 1 3%
Denmark 1 3%
Saudi Arabia 1 3%
Brazil 1 3%
Unknown 34 89%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 24%
Student > Bachelor 5 13%
Student > Doctoral Student 4 11%
Student > Ph. D. Student 3 8%
Other 2 5%
Other 6 16%
Unknown 9 24%
Readers by discipline Count As %
Medicine and Dentistry 11 29%
Agricultural and Biological Sciences 6 16%
Biochemistry, Genetics and Molecular Biology 6 16%
Immunology and Microbiology 2 5%
Veterinary Science and Veterinary Medicine 1 3%
Other 1 3%
Unknown 11 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 March 2015.
All research outputs
#14,387,227
of 25,371,288 outputs
Outputs from Critical Care
#4,748
of 6,554 outputs
Outputs of similar age
#186,879
of 395,397 outputs
Outputs of similar age from Critical Care
#394
of 466 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,554 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.8. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 395,397 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 466 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.