Metabolic & Cardiometabolic
MTHFR C677T increases homocysteine
Part of: • MTHFR C677T
📅 Last reviewed: 2026-07-15 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Population patterns (Observational)
How the studies fall
What the evidence shows
The MTHFR C677T TT genotype is associated with higher serum homocysteine in women with PCOS (reduced enzyme activity → impaired homocysteine remethylation). Mechanistic basis for the vascular/stroke-risk thread.
The evidence (11)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Song J et al 2026 · study_type: observational | observational | supports | medium | N. China diabetic-nephropathy cohort (n=397): Hcy 17.29±8.95 (TT) vs 13.08±6.20 (CT) vs 12.65±4.35 µmol/L (CC), p<0.001; TT genotype 12.7x risk of nephropathy vs CC. |
| Zhao J, Li X, Chen Q 2024 · Gene | observational | supports | moderate | [FT-verified] Zhao 2024 PCOS n=104 TT Hcy>CT>CC; confirms scoped PCOS appraisal |
| Zhou R et al 2025 · study_type: observational | observational | supports | moderate | Large infertility cohort (n=6344): serum Hcy significantly higher in MTHFR 677CT and TT vs CC (p<0.001 for both); Hcy mediated 15.8% (CT) and 41.6% (TT) of the genotype–vitamin-D-deficiency association. |
| Shareef ZA et al 2025 · study_type: observational | observational | supports | moderate | Iraqi Kurdish T2DM cross-sectional: TT genotype associated with higher homocysteine (22.08±5.74 µmol/L) and lower HDL-C vs other genotypes; CC/CT comparator values not given in abstract. |
| Oliveira IO et al] # corrected 2026-08-17 from PubMed; was [et al. 2017 · Eur J Clin Nutr | observational | supports | moderate | MTHFR C677T TT raises homocysteine (modified by smoking/alcohol). |
| Oliveira APG et al] # corrected 2026-08-17 from PubMed; was [et al. 2024 · Diagn Microbiol Infect Dis | observational | supports | moderate | [FT-verified] Oliveira 2024 H.pylori n=168 TT assoc higher Hcy; independent beyond PCOS |
| Jin M et al 2022 · study_type: observational | observational | supports | medium | Han Chinese case-control (1810 LAAIS cases, 1765 controls): plasma Hcy genotype-dependent trend TT > CT > CC (no exact values/CI given in abstract). |
| Oh S et al 2026 · study_type: observational | observational | supports | low | Case report: homozygous C677T, plasma Hcy >50µmol/L with concurrent folate deficiency; severe thrombosis; Hcy improved with folate/B6 repletion. |
| Akácsos-Szász OZ et al 2026 · study_type: observational | observational | supports | low | PAD cohort, severe cases (n=31): homozygous MTHFR mutation carriers had significantly higher homocysteine than normal-allele carriers (mean overall Hcy 17.7±10.6 µmol/L; p=0.0334). |
| Li Y et al 2025 · study_type: observational | observational | supports | low | Spontaneous-abortion cohort (474 women, 235 men): female TT carriers had significantly higher HCY than CC/CT (P=0.002); no such difference in males. |
| Daghlas I et al 2026 · study_type: observational | observational | supports | moderate | Mendelian-randomization/genetic-association analysis (n=1210 for Hcy-genotype association): C677T associated with higher homocysteine; used as instrument scaling MS risk per SD Hcy increase (OR 0.73, CI 0.66-0.79). |
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