Devlin - Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly

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Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population 1–3 Angela M Devlin, Robert Clarke, Jacqueline Birks, John Grimley Evans, and Charles H Halsted ABSTRACT Background: Homocysteine concentrations are influenced by vi- tamin status and genetics, especially several polymorphisms in folate-metabolizing genes. Objective: We examined the interactions and associations with serum total homocysteine (tHcy) and folate concentrations of poly- morphisms in the following folate-metabolizing genes: methyl- enetetrahydrofolate reductase ( MTHFR ), reduced folate carrier 1 ( RFC1 ), and glutamate carboxypeptidase II ( GCPII ). Design: Healthy volunteers (436 men and 606 women; mean age: 77.9 y) were randomly selected from among residents of Oxford, United Kingdom. We determined the individual effects and interac- tions of the MTHFR 677C 3 T, MTHFR 1298A 3 C, RFC1 80G 3 A, and GCPII 1561C 3 T polymorphisms on serum tHcy and folate concentrations. Results: Subjects with the MTHFR 677TT genotype had higher serum tHcy concentrations than did those with the MTHFR 677CC genotype( P ± 0.001),andthiseffectwasgreaterinsubjectswithlow serum folate status ( P for interaction ² 0.026). The MTHFR 1298A 3 C, RFC1 80G 3 A, and GCPII 1561C 3 T polymorphisms had no individual effects on serum tHcy or folate concentrations. There was no interactive effect of the MTHFR 677C 3 T and MTHFR 1298A 3 C polymorphisms on tHcy concentrations. An interaction( P ² 0.05)wasobservedbetweenthe MTHFR677TT and RFC1 80GG genotypes, whereby persons with this genotype com- bination had a mean ( ³ SEM) serum tHcy concentration (18.5 ³ 1.2 ± mol/L) that was 5.1 mol/L greater than the mean value of 13.4 ³ 0.2 mol/L for the whole population. Conclusions: Folate and tHcy concentrations were not affected individually by the MTHFR 1298A 3 C, RFC1 80G 3 A, or GCPII 1561C 3 T polymorphisms or by combinations of the MTHFR 677C 3 T and MTHFR 1298A 3 C genotypes. An interaction be- tween the MTHFR 677TT and RFC1 80GG genotypes was observed whereby persons with this combination had higher serum tHcy. Am J Clin Nutr 2006;83:708–13. KEY WORDS Serum folate, serum total homocysteine, meth- ylenetetrahydrofolate reductase 677C 3 T polymorphism, methyl- enetetrahydrofolate reductase 1298A 3 C polymorphism, reduced folate carrier 1 80G 3 A polymorphism, glutamate carboxypepti- dase II 1561C 3 T polymorphism, elderly INTRODUCTION Hyperhomocysteinemia is an independent risk factor for car- diovascular disease (1–3), Alzheimer disease (4, 5), cognitive impairment(6),andosteoporoticfractures(7).Folatestatusisthe most important vitamin determinant of blood total homocysteine (tHcy) concentrations (8), and several polymorphisms in genes for enzymes required for folate metabolism have been shown to be associated with elevations in tHcy.
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This note was uploaded on 11/21/2010 for the course NUT 72880 taught by Professor Clifford during the Fall '10 term at UC Davis.

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Devlin - Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly

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