Genetic Defects as Important Factors for Moderate Hyperhomocysteinemia
The genes for the enzymes methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS), methionine synthase reductase (MSR) and cytathionine-Β-synthase (CBS) play an important role in homocysteine metabolism. Rare mutations in these genes cause severe hyperhomocysteinemia and clinical sympt...
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Published in | Clinical chemistry and laboratory medicine Vol. 39; no. 8; pp. 698 - 704 |
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Main Authors | , , , , , , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
Berlin
Walter de Gruyter
01.08.2001
New York, NY |
Subjects | |
Online Access | Get full text |
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Summary: | The genes for the enzymes methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS), methionine synthase reductase (MSR) and cytathionine-Β-synthase (CBS) play an important role in homocysteine metabolism. Rare mutations in these genes cause severe hyperhomocysteinemia and clinical symptoms. Growing interest has focused on common mutations with moderate effects on homocysteine levels. We studied 280 subjects of different age groups for the following mutations: MTHFR677C→T and 1298A→C, MS2756A→G, MSR66A→G and the 68 bp insertion in the CBS gene. The median value for homocysteine increased significantly with age (median homocysteine levels: 7.5, 12.4 and 16.5 μmol/l in the age groups 20–43, 65–75 and 85–96 years, respectively). The genotypes of the MTHFR677C→T mutation were associated with differences in plasma homocysteine levels, but without reaching significance. Individuals homozygous for the MTHFR677C→T mutation had a 2.3 μmol/l higher median homocysteine level compared to individuals with the wild-type allele. This effect was pronounced in combination with low folate levels and abolished with higher folate in plasma. For the other three mutations no association with homocysteine values could be determined. The analysis of homocysteine metabolite cystathionine by backward regression analysis revealed a significant correlation of the MS2756A→G mutation with cystathionine level. This increase could indicate a disturbed remethylation. In summary, larger and homogeneous study populations are necessary to quantify the small effects of common mutations on homocysteine levels. This may also be the reason that no effects of genetic interactions between two genotypes were observed. |
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Bibliography: | istex:A3F38F02016407B8E046A578B94417F55005A5A3 cclm.2001.115.pdf ark:/67375/QT4-V682F411-3 ArticleID:cclm.39.8.698 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1434-6621 1437-4331 |
DOI: | 10.1515/CCLM.2001.115 |