The effect of MTHFR c.677C>T on plasma homocysteine levels depends on health, age and smoking
Bibliographic record
Abstract
PURPOSE: The role of homocysteine in the pathogenesis of arteriosclerosis and stroke is under debate. It is important to determine the interplay of factors that influence homocysteine plasma levels, such as age, gender, smoking and the genetic background. The T-allele of the common variant methylenetetrahydrofolate reductase (MTHFR) c.677C > T is the most prevalent known genetic cause of elevated plasma homocysteine levels, but the association of this allele with vascular disease has been controversial. The aim of the present study was to examine whether the influence of MTHFR c.677C > T on homocysteine levels depends on individual factors. METHODS: From an ongoing study on atherosclerosis, we analyzed 523 Caucasian individuals, including patients with cerebrovascular disease (n=141), their healthy spouses (n=106) and the offspring (n=276). ANOVA and regression analyses were employed to separately analyze the effect of MTHFR c.677C > T on homocysteine levels in patients, spouses and offspring as well as in subgroups defined by age, gender and smoking. RESULTS: MTHFR c.677C > T was associated with homocysteine plasma levels in the study sample (P < 0.001), but not in the patients with cerebrovascular disease, if analyzed separately. Analyses of subgroups divided by the age of 55 years revealed that the MTHFR c.677 C > T genotype was associated with homocysteine plasma levels in the younger (P < 0.001), but not in the older individuals. In addition, if individuals with at least less than ten cigarette package years were analyzed separately, MTHFR c.677C > T was associated with plasma homocysteine levels only in the group with the lower cigarette consumption (P=0.002). CONCLUSION: In our study, the association of the MTHFR c.677C > T genotype with plasma homocysteine levels was weakened by other factors that impact homocysteine levels. The effect of MTHFR c.677C > T on plasma homocysteine levels may, thus, be of major importance for healthy, young, non-smoking persons. Such specifications may explain the controversial results of epidemiological studies on the relevance of MTHFR c.677C > T.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".