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.
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.
Authors: M Hattori; A Fujiyama; T D Taylor; H Watanabe; T Yada; H S Park; A Toyoda; K Ishii; Y Totoki; D K Choi; Y Groner; E Soeda; M Ohki; T Takagi; Y Sakaki; S Taudien; K Blechschmidt; A Polley; U Menzel; J Delabar; K Kumpf; R Lehmann; D Patterson; K Reichwald; A Rump; M Schillhabel; A Schudy; W Zimmermann; A Rosenthal; J Kudoh; K Schibuya; K Kawasaki; S Asakawa; A Shintani; T Sasaki; K Nagamine; S Mitsuyama; S E Antonarakis; S Minoshima; N Shimizu; G Nordsiek; K Hornischer; P Brant; M Scharfe; O Schon; A Desario; J Reichelt; G Kauer; H Blocker; J Ramser; A Beck; S Klages; S Hennig; L Riesselmann; E Dagand; T Haaf; S Wehrmeyer; K Borzym; K Gardiner; D Nizetic; F Francis; H Lehrach; R Reinhardt; M L Yaspo Journal: Nature Date: 2000-05-18 Impact factor: 49.962
Authors: T J Hassold; L C Burrage; E R Chan; L M Judis; S Schwartz; S J James; P A Jacobs; N S Thomas Journal: Am J Hum Genet Date: 2001-07-05 Impact factor: 11.025
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