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Cited by 36Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchHereditary Neurological Disorders

Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes

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Matsukawa, Takashi, Asheuer, Muriel, Takahashi, Yuji, Goto, Jun, Suzuki, Yasuyuki, Shimozawa, Nobuyuki, Takano, Hiroki, Onodera, Osamu +3 more·2011·neurogenetics
DOI 10.1007/s10048-010-0253-6PMC PMC3029816
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Abstract

Adrenoleukodystrophy (ALD) is an X-linked disorder affecting primarily the white matter of the central nervous system occasionally accompanied by adrenal insufficiency. Despite the discovery of the causative gene, ABCD1, no clear genotype-phenotype correlations have been established. Association studies based on single nucleotide polymorphisms (SNPs) identified by comprehensive resequencing of genes related to ABCD1 may reveal genes modifying ALD phenotypes. We analyzed 40 Japanese patients with ALD. ABCD1 and ABCD2 were analyzed using a newly developed microarray-based resequencing system. ABCD3 and ABCD4 were analyzed by direct nucleotide sequence analysis. Replication studies were conducted on an independent French ALD cohort with extreme phenotypes. All the mutations of ABCD1 were identified, and there was no correlation between the genotypes and phenotypes of ALD. SNPs identified by the comprehensive resequencing of ABCD2, ABCD3, and ABCD4 were used for association studies. There were no significant associations between these SNPs and ALD phenotypes, except for the five SNPs of ABCD4, which are in complete disequilibrium in the Japanese population. These five SNPs were significantly less frequently represented in patients with adrenomyeloneuropathy (AMN) than in controls in the Japanese population (p=0.0468), whereas there were no significant differences in patients with childhood cerebral ALD (CCALD). The replication study employing these five SNPs on an independent French ALD cohort, however, showed no significant associations with CCALD or pure AMN. This study showed that ABCD2, ABCD3, and ABCD4 are less likely the disease-modifying genes, necessitating further studies to identify genes modifying ALD phenotypes.

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  • Attempts to identify a modifier variant among 16 candidate genes, including some involved in inflammatory processes, had no success.

    “Although a large segregation analysis suggested the presence of a single “major” autosomal modifier locus [111], attempts to identify a modifier variant among 16 candidate genes, including some involved in inflammatory processes, had no success [15,112,113,114,115,116], as reviewed in [15].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [115]

    The Results and Discussion report an unsuccessful search for consistently associated modifier SNPs in ABCD2, ABCD3, and ABCD4. This paper does not establish the citing sentence’s total of 16 candidate genes or identify the genes it tested as involved in inflammatory processes. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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  • Two independent association studies comparing ABCD2 and ABCD3 polymorphisms with different clinical phenotypes failed to determine significant correlations.

    “However, two independent association studies comparing ABCD2 and ABCD3 polymorphisms with different clinical phenotypes failed to determine significant correlations.98,99”

    From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [99]

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Authors
Matsukawa, T., Asheuer, M., Takahashi, Y., Goto, J., Suzuki, Y., Shimozawa, N., Takano, H., Onodera, O., Nishizawa, M., Aubourg, P., & Tsuji, S.
Affiliations
  • The University of Tokyo (JP)
  • Inserm (FR)
  • Gifu University (JP)
  • Niigata University (JP)
Corresponding author
Tsuji, Shoji
ORCID
Venue
neurogenetics
Publisher
Springer Science and Business Media LLC
Published
2010-07-27
Volume
12
Issue
1
Pages
41-50
ISSN
  • 1364-6745 (ISSN-L)
  • 1364-6753
DOI
10.1007/s10048-010-0253-6
PMC
PMC3029816
OpenAlex
W2030941134
Cited by
36
References
5
Citations by year
2025: 5 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 5
FWCI
1.61
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Neurogenetics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Ministry of Education, Culture, Sports, Science and Technology
  • Ministry of Health, Labour and Welfare
  • Japan Society for the Promotion of Science (21591318)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
X-linked adrenoleukodystrophy, ABCD1, ABCD2, ABCD3, ABCD4, single nucleotide polymorphisms, genotype-phenotype correlation, adrenomyeloneuropathy, childhood cerebral adrenoleukodystrophy, disease-modifying genes, genetic association, Japanese patients
MeSH terms
ATP Binding Cassette Transporter, Subfamily D, ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Adult, Alleles, Base Sequence, Child, DNA Mutational Analysis, France, Gene Frequency, Humans, Japan, Mutation, Linkage Disequilibrium, DNA Primers, ATP-Binding Cassette Transporters, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Asian People, Genome-Wide Association Study, Genetic Association Studies

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