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01-04-2017 | Original Article

ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI

Authors: Ruchira M. Jha, Ava M. Puccio, David O. Okonkwo, Benjamin E. Zusman, Seo-Young Park, Jessica Wallisch, Philip E. Empey, Lori A. Shutter, Robert S. B. Clark, Patrick M. Kochanek, Yvette P. Conley

Published in: Neurocritical Care | Issue 2/2017

Abstract

Objective

Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (ABCC8) on the development of CE. We hypothesize that ABCC8 single nucleotide polymorphisms (SNPs) are predictive of CE.

Methods

DNA was extracted from 385 patients. SNPs in ABCC8 were genotyped using the Human Core Exome v1.2 (Illumina). CE measurements included acute CT edema, mean and peak intracranial pressure (ICP), and need for decompressive craniotomy.

Results

Fourteen SNPs with minor allele frequency >0.2 were identified. Four SNPS rs2283261, rs3819521, rs2283258, and rs1799857 were associated with CE measures. In multiple regression models, homozygote-variant genotypes in rs2283261, rs3819521, and rs2283258 had increased odds of CT edema (OR 2.45, p = 0.007; OR 2.95, p = 0.025; OR 3.00, p = 0.013), had higher mean (β = 3.13, p = 0.000; β = 2.95, p = 0.005; β = 3.20, p = 0.008), and peak ICP (β = 8.00, p = 0.001; β = 7.64, p = 0.007; β = 6.89, p = 0.034). The homozygote wild-type genotype of rs1799857 had decreased odds of decompressive craniotomy (OR 0.47, p = 0.004).

Conclusions

This is the first report assessing the impact of ABCC8 genetic variability on CE development in TBI. Minor allele ABCC8 SNP genotypes had increased risk of CE, while major SNP alleles were protective—potentially suggesting an evolutionary advantage. These findings could guide risk stratification, treatment responders, and the development of novel targeted or gene-based therapies against CE in TBI and other neurological disorders.

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Title: ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI
Authors: Ruchira M. Jha
Ava M. Puccio
David O. Okonkwo
Benjamin E. Zusman
Seo-Young Park
Jessica Wallisch
Philip E. Empey
Lori A. Shutter
Robert S. B. Clark
Patrick M. Kochanek
Yvette P. Conley
Publication date: 01-04-2017
Publisher: Springer US
Published in: Neurocritical Care / Issue 2/2017
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI: https://doi.org/10.1007/s12028-016-0309-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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