ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study.

ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Research Abstract Details 

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ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Abstract Text:

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease characterised by progressive degeneration of motor neurons in the brain and spinal cord. ALS is thought to be multifactorial, with both environmental and genetic causes. Our aim was to identify genetic variants that predispose for sporadic ALS. METHODS: We did a three-stage genome-wide association study in 461 patients with ALS and 450 controls from The Netherlands, using Illumina 300K single-nucleotide polymorphism (SNP) chips. The SNPs that were most strongly associated with ALS were analysed in a further 876 patients and 906 controls in independent sample series from The Netherlands, Belgium, and Sweden. We also investigated the possible pathological functions of associated genes using expression data from whole blood of patients with sporadic ALS and of control individuals who were included in the genome-wide association study. FINDINGS: A genetic variant in the inositol 1,4,5-triphosphate receptor 2 gene (ITPR2) was associated with ALS (p=0.012 after Bonferroni correction). Combined analysis of all samples (1337 patients and 1356 controls) confirmed this association (p=3.28x10(-6), odds ratio 1.58, 95% CI 1.30-1.91). ITPR2 expression was greater in the peripheral blood of 126 ALS patients than in that of 126 healthy controls (p=0.00016). INTERPRETATION: Genetic variation in ITPR2 is a susceptibility factor for ALS. ITPR2 is a strong candidate susceptibility gene for ALS because it is involved in glutamate-mediated neurotransmission, is one of the main regulators of intracellular calcium concentrations, and has an important role in apoptosis.

ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Publishing Authors By Initials

For similar genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research abstracts see: genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research

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ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Lancet neurology

VOLUME: 6

Page Numbers: 869-77

Journal Abbreviation:

ISSN: 1474-4422

DAY: 3

MONTH: Oct

YEAR: 2007

ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101139309

ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Keywords Mesh Terms:

KEYWORDS: Polymorphism, Single Nucleotide

MESH TERMS: genetics

Chemical & Substance for Abstract: ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Information

Substance Name: Inositol 1,4,5-Trisphosphate Receptors

Registry Number: 0

Grant and Affiliation Information for ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study.

AFFILIATION: Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.

Country: England

AGENCY: United States NIMH

GRANT: MH078075

ACRONYM: MH

MEDLINETA: Lancet Neurol

REFSOURCE: Lancet Neurol. 2007 Oct;6(10):841-3

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