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Cited by 45Folate and B Vitamins ResearchDown syndrome and intellectual disability researchDementia and Cognitive Impairment Research

Homocysteine and related genetic polymorphisms in down’s syndrome IQ.

Open access
Gueant, J-L·2005·Journal of Neurology, Neurosurgery & Psychiatry
DOI 10.1136/jnnp.2004.039875PMC PMC1739618
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Abstract

OBJECTIVE: Down's syndrome (DS) is the most frequent genetic cause of Alzheimer-type dementia. Its metabolic phenotype involves an increased trans-sulphuration of homocysteine. The aim of the present study was to investigate the influence of homocysteinaemia (t-Hcys), folate, vitamin B(12), and related polymorphisms on intelligence quotient (IQ) in DS. METHODS: The IQ of 131 patients with trisomy 21 from a specialist centre in Sicily was determined and classified according to DMS-IV. The effects of age, folate, vitamin B(12), t-Hcys, and genetic polymorphisms on IQ were evaluated separately and in combination using regression analyses. RESULTS: IQ was significantly lower in DS patients with t-Hcys >7.5 micromol/l (median) and in those who were carriers of methylenetetrahydrofolate reductase (MTHFR) 677 T allele and of methylenetetrahydrofolate reductase 677 T and transcobalamin 776 G combined alleles (p = 0.0013, p = 0.0165, and p = 0.0074, respectively). The IQ correlated significantly with t-Hcys and folate in single and multiple regression analyses, independently of age. In addition, t-Hcys >9.6 micromol/l (upper quartile) was found to be associated with low IQ (<40, median of study group) with an odds ratio of 2.61 (p = 0.0203). The odds ratio was increased by threefold in carriers of MTHFR 677T allele. The MTHFR 677T allele/transcobalamin 776 G allele combination was associated with the risk of DS patients to have an IQ less that the median with an odds ratio of 2.68 (95% CI 1.26 to 5.70, p = 0.0104). CONCLUSION: This study found evidence of an association between t-Hcys and MTHFR 677 T and transcobalamin 776 G alleles with IQ in patients with DS. The association may be related to a defective remethylation of homocysteine, affecting IQ.

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  • The intellectual disability in Down syndrome ranges from moderate to severe as measured by intelligence quotient (IQ 10-70) with a median IQ of 40.

    “The ID in DS ranges from moderate to severe as measured by intelligence quotient (IQ 10–70) with a median IQ of 40 (Guéant et al., 2005).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Guéant et al., 2005

    The Results report IQs of 10–70 among 131 patients with Down syndrome, with a median of 40. But the same section identifies patients with IQs below 25 as having profound, rather than severe, intellectual disability; the stated severity range therefore omits a category present in the sample. (LLM, conf=0.90)

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Cited by

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Authors
Gueant, J.-L.
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
2005-05-01
Volume
76
Issue
5
Pages
706-709
ISSN
0022-3050 (ISSN-L)
DOI
10.1136/jnnp.2004.039875
PMC
PMC1739618
OpenAlex
W2067535022
Cited by
45
References
1
Citations by year
2025: 2 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 1
FWCI
2.45
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Down syndrome, homocysteine, intelligence quotient, folic acid, vitamin B12, homocysteine remethylation, genetic polymorphism, cognitive impairment
MeSH terms
Alleles, Alzheimer Disease, Apolipoproteins E, Down Syndrome, Folic Acid, Homocysteine, Humans, Intelligence, Karyotyping, Polymorphism, Genetic, Transcobalamins, Vitamin B 12, Diagnostic and Statistical Manual of Mental Disorders, Methylenetetrahydrofolate Reductase (NADPH2)

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