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ORIGINAL RESEARCH COMMUNICATION |
1 From the Faculté de Médecine, Laboratory of Medical Biochemistry, Vandoeuvre-Lès-Nancy, France (NF-E, FB, and JPN); the ISAB, Laboratory of Nutritional Genomics, Beauvais, France (AC); the Jérôme Lejeune Medical Center, Paris (CM, HB, and M-OR); INSERM U525 and CMP, Nancy, France (BH and DL); and the Division of Medical Genetics, Department of Medicine, McGill University, Montréal, Quebec (DSR)
Background:The effects of supplementation with B vitamins and of common polymorphisms in genes involved in homocysteine metabolism on plasma total homocysteine (tHcy) concentrations in trisomy 21 are unknown.
Objectives:We aimed to determine the effects of orally administered folic acid and of folic acid combined with vitamin B-12, vitamin B-6, or both on tHcy in adults with trisomy 21. The study was also intended to analyze the possible influence of gene polymorphisms.
Design:One hundred sixty adults with trisomy 21 and 160 healthy, unrelated subjects aged 26 ± 4 y were included. Plasma tHcy, red blood cell folate, serum folate, and vitamin B-12 were measured. Genotyping for the common methylenetetrahydrofolate reductase (MTHFR) 677C
T, MTHFR 1298AC, cystathionine ß-synthase 844Ins68, methionine synthase 2756AC, methionine synthase reductase 66AG, and reduced folate carrier 80GA polymorphisms was carried out.
Results:The mean tHcy concentration (9.8 ± 0.7 µmol/L) of cases who did not use vitamins was not significantly different from that of controls (9.4 ± 0.3 µmol/L). Plasma tHcy concentrations (7.6 ± 0.3 mmol/L) in cases who used folic acid were significantly lower than in cases who did not. Folic acid combined with vitamin B-12 did not significantly change tHcy concentrations compared with those in cases who used only folic acid. Folic acid combined with vitamins B-6 and B-12 significantly lowered tHcy (6.5 ± 0.5 µmol/L). The difference in tHcy according to MTHFR genotype was not significant. However, tHcy concentrations were slightly higher in TT homozygotes among the controls but not among the cases.
Conclusion:This study provides information on the relation between several polymorphisms in genes involved in homocysteine and folate metabolism in adults with trisomy 21.
Key Words: Down syndrome • trisomy 21 • folate • homocysteine • polymorphism • CBS • MTR • MTRR • MTHFR • RFC • vitamin B-12 • vitamin B-6
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