ArticleProceedings of the National Academy of Sciences of the United States of America2009
Chromogranin B P413L variant as risk factor and modifier of disease onset for amyotrophic lateral sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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27 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Peptidomic analysis of CSF reveals new biomarker candidates for amyotrophic lateral sclerosis.EMBO molecular medicine · 2025Article
- Molecular requirements of chromogranin B for the long-sought anion shunter of regulated secretion.International journal of biological macromolecules · 2025Article
- Article
- Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.Nature reviews. Neurology · 2024Review
- Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes.Nature communications · 2024Article
- Article
- The Role of Sex and Sex Hormones in Neurodegenerative Diseases.Endocrine reviews · 2020Review
- Targeted Multiple Reaction Monitoring Analysis of CSF Identifies UCHL1 and GPNMB as Candidate Biomarkers for ALS.Journal of molecular neuroscience : MN · 2019Article
- Younger age of onset in familial amyotrophic lateral sclerosis is a result of pathogenic gene variants, rather than ascertainment bias.Journal of neurology, neurosurgery, and psychiatry · 2019Article
- Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes.Life science alliance · 2018Article
- Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis.Scientific reports · 2018Article
- Genetics of Amyotrophic Lateral Sclerosis.Cold Spring Harbor perspectives in medicine · 2018Review
- Sex-dependent effects of chromogranin B P413L allelic variant as disease modifier in amyotrophic lateral sclerosis.Human molecular genetics · 2016Article
- Familial Amyotrophic Lateral Sclerosis.Neurologic clinics · 2015Review
- Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges.Brain research · 2015Review
- Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease.Human genetics · 2013Review
- Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.Neurobiology of aging · 2013Article
- Biomarkers in frontotemporal lobar degenerations--progress and challenges.Progress in neurobiology · 2011Review
- The extended granin family: structure, function, and biomedical implications.Endocrine reviews · 2011Review
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, chromogranins were reported to interact specifically with mutant forms of superoxide dismutase that are linked to amyotrophic lateral sclerosis (ALS). This interaction led us to analyze the frequencies of sequence variants of the CHGB gene in ALS patients and matched controls from three different countries. Of particular interest was the finding of the P413L CHGB variant present in 10% of ALS patients (n = 705) as compared to 4.5% in controls (n = 751), conferring a 2.2-fold greater relative risk to develop the disease (P < 0.0001). This effect was mainly contributed by the samples of French origin that yielded a frequency of the P413L variation at 17% in ALS (n = 289) and 5% in controls (n = 448), conferring a 3.3-fold greater risk to develop ALS. Furthermore, the P413L CHGB variant is associated with an earlier age of onset by almost a decade in both sporadic ALS and familial ALS cases. Genetic variation influencing age of onset in ALS had not previously been reported. Expression of fusion CHGB-EGFP constructs in SHSY-5Y cells revealed that the P413L variation can cause defective sorting of CHGB into secretory granules. The finding that CHGB may act as a susceptibility gene and modifier of onset in ALS is consistent with the emerging view that dysfunction of the secretory pathway may contribute to increased vulnerability of motor neurons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.