RGD Reference Report - ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. - Rat Genome Database

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

Authors: Van Es, MA  Van Vught, PW  Blauw, HM  Franke, L  Saris, CG  Andersen, PM  Van Den Bosch, L  De Jong, SW  Van 't Slot, R  Birve, A  Lemmens, R  De Jong, V  Baas, F  Schelhaas, HJ  Sleegers, K  Van Broeckhoven, C  Wokke, JH  Wijmenga, C  Robberecht, W  Veldink, JH  Ophoff, RA  Van den Berg, LH 
Citation: van Es MA, etal., Lancet Neurol. 2007 Oct;6(10):869-77.
RGD ID: 6482791
Pubmed: PMID:17827064   (View Abstract at PubMed)
DOI: DOI:10.1016/S1474-4422(07)70222-3   (Journal Full-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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
amyotrophic lateral sclerosis susceptibilityIAGP 6482791DNA:snp:intron:g.26636386A>G rs2306677 (human)RGD 
amyotrophic lateral sclerosis susceptibilityISOITPR2 (Homo sapiens)6482791; 6482791DNA:snp:intron:g.26636386A>G rs2306677 (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Motor neuron atrophy  IAGP 6482791DNA:snp:intron:g.26636386A>G (rs2306677)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Itpr2  (inositol 1,4,5-trisphosphate receptor, type 2)

Genes (Mus musculus)
Itpr2  (inositol 1,4,5-triphosphate receptor 2)

Genes (Homo sapiens)
ITPR2  (inositol 1,4,5-trisphosphate receptor type 2)


Additional Information