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Genetic defects as important factors for moderate hyperhomocysteinemia
J Geisel1, I Zimbelmann, H Schorr
1Department of Clinical Chemistry, Hospital of the University of Saarland, Homburg, Germany. kchjgei@med-rz.uni-sb.de
Clinical Chemistry and Laboratory Medicine
|October 11, 2001
Summary
Common gene mutations have minor effects on homocysteine levels, with MTHFR677C-->T showing a slight increase, especially with low folate. Larger studies are needed to confirm these findings.
Area of Science:
- Biochemistry
- Genetics
- Nutritional Science
Background:
- Homocysteine metabolism is crucial, involving enzymes like methylenetetrahydrofolate reductase (MTHFR).
- Rare mutations cause severe hyperhomocysteinemia; common mutations' moderate effects are of growing interest.
- Age significantly impacts homocysteine levels, increasing with age.
Purpose of the Study:
- To investigate the association between common genetic mutations in homocysteine metabolism genes and plasma homocysteine levels.
- To examine the influence of MTHFR, MS, MSR, and CBS gene mutations on homocysteine and cystathionine levels.
- To explore potential interactions between genotypes and their effect on homocysteine levels.
Main Methods:
- Studied 280 subjects across different age groups.
- Genotyped for MTHFR (677C-->T, 1298A-->C), MS (2756A-->G), MSR (66A-->G), and CBS (68 bp insertion) mutations.
- Analyzed plasma homocysteine and cystathionine levels in relation to genotypes and age.
Main Results:
- Median homocysteine levels significantly increased with age.
- MTHFR677C-->T genotypes showed a trend towards higher homocysteine, particularly in homozygotes (2.3 micromol/l higher median), exacerbated by low folate.
- MS2756A-->G mutation correlated with increased cystathionine, suggesting disturbed remethylation; other mutations showed no significant association with homocysteine.
Conclusions:
- Common mutations have small effects on homocysteine levels, requiring larger, homogeneous populations for precise quantification.
- The MTHFR677C-->T mutation's effect is modulated by folate status.
- Further research is needed to understand genetic interactions and their impact on homocysteine metabolism.