677TT polymorphism of methylenetetrahydrofolate reductase in combination with low serum vitamin B12 is associated with coronary in-stent restenosis.
BACKGROUND
Recent studies have shown that a common mutation (nucleotide 677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to a mild rise in plasma homocysteine levels and increase the incidence of coronary artery disease. Therefore, this study was designed to further investigate whether the effects of MTHFR 677 C to T mutation, plasma homocysteine, serum vitamin B12, and folate can influence restenosis after successful coronary stenting.


RESULTS
We investigated 260 patients each with a lesion after successful coronary stent placement. All patients received a repeated angiography after 6 months, or earlier if clinically indicated. Angiographic in-stent restenosis (ISR) was defined as >or=50% diameter stenosis at follow-up. Genotyping for MTHFR was based on a polymerase chain reaction technique. Also fasting plasma homocysteine, vitamin B12, and folate levels were measured at the same time. The ISR rate was higher among the patients with the TT genotype than in those with the non-TT genotypes (64.0% versus 32.9%, P=0.002). There was no significant difference in plasma homocysteine levels among patients with the TT genotype and patients with the non-TT genotypes (15.9+/-7.6 versus 15.5+/-6.6 micromol/L, P=0.75). However, among the patients with the TT genotype, those with higher plasma homocysteine levels (>or=12 micromol/L) demonstrated a significantly higher ISR rate (75.0% versus 33.5%, P=0.001). Logistic regression analysis revealed that the combined presence of the MTHFR TT genotype and lower than average serum vitamin B12 (>or=550 pg/mL) resulted in the most significant difference in the risk of ISR (OR=3.57, CI=1.51-8.46, P=0.004; OR=2.36, CI=1.35-4.15, P=0.003).


CONCLUSIONS
MTHFR 677TT polymorphism and low serum vitamin B12 each individually increased the risk of coronary ISR. Furthermore, the combination of these parameters resulted in a greater increase in risk.
Division of Cardiology, Department of Medicine, LoTung Poh-Ai Hospital, Yilan County, Taiwan.
Sheng-Liang
SL
Chung
Kuan-Rau
KR
Chiou
Min-Ji
MJ
Charng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015607:Stents; D013624:Taiwan; D014805:Vitamin B 12 / Q000097:blood*
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12