五-甲基四氫葉酸還原酶基因多型性及B-維生素與血漿同半胱胺酸濃度及冠狀動脈心臟病危險因子之關係

5-Methylenetetrahydrofolate reductase gene polymorphism and B-vitamins in relation to plasma homocysteine concentration and risk factors of coronary artery disease

林娉婷(Ping-Ting Lin)

指導教授 ： 黃怡嘉

中山醫學大學/健康管理學院/營養學研究所/博士(2007年)

https://doi.org/10.6834/CSMU.2007.00070

摘要

本研究探討五甲基四氫葉酸還原酶(MTHFR 677C->T）基因多型性、B-維生素（葉酸、維生素B-6、B-12）營養狀況與高同半胱胺酸血症、高血脂、高血壓及冠狀動脈心臟病（CAD）危險性之關係；及給予低劑量葉酸補充劑後對於降低血漿同半胱胺酸之效果。本研究共募集184位CAD受試者及516位健康受試者，測量血脂質、血漿同半胱胺酸、B-維生素濃度及分析MTHFR 677C->T之基因多型性。根據MTHFR基因型，追蹤46位CAD病人，並隨機分配給與安慰劑（n = 22）及葉酸補充劑（400ug/天, n = 24）。結果顯示攜帶677TT基因型受試者之血漿同半胱胺酸濃度顯著高於677CC基因型受試者。調整CAD危險因子後，發現MTHFR 677C->T基因多型性對血漿同半胱胺酸濃度及血壓有顯著的相關性。當血漿同半胱胺酸濃度（>= 12.5umo/L）時會增加罹患CAD的危險對比值（OR, 3.490; 95% CI, 1.233 – 9.877），但MTHFR 677C->T基因多型性對罹患CAD之危險對比值無顯著影響。當受試者維生素B-6濃度小於30 nmol/L時血脂質濃度顯著上升且顯著增加罹患CAD (OR, 1.85; 95% CI, 1.16 – 2.95)及高血壓（OR, 16.44, P < 0.001）的危險性。給予低劑量葉酸介入8週後，並無顯著降低CAD受試者血漿同半胱胺酸濃度，但可顯著降低高同半胱胺酸血症病人血漿同半胱胺酸濃度，尤其是攜帶677TT基因型的CAD病人。677TT基因型會顯著增加血漿同半胱胺酸濃度，低維生素B-6濃度（< 30 nmol/L）與高血脂及高血壓有顯著的相關性，而同半胺酸為CAD的危險因子；高同半酸血症之CAD病人使用低劑量葉酸補充劑（400ug/天）可顯著降低胱胺酸濃度。

關鍵字

五甲基四氫葉酸還原酶葉酸 ； 維生素B-6 ； 葉酸補充劑 ； 高同半胱胺酸血症 ； 高血脂 ； 高血壓 ； 冠狀動脈疾病

並列摘要

The purposes of this study were to investigate B-vitamins (folate, vitamin B-6 and B-12) status, methylenetetrahydrofolate reductase (MTHFR 677C->T) gene polymorphism, homocysteine in relation to the risk of hyperlipidemia, hypertension and coronary artery disease (CAD). Furthermore, the effect of a low oral dose of folic acid on lowering the plasma homocysteine concentration in response to the MTHFR 677C->T genotypes in patients with CAD was also evaluated. Patients who were identified by cardiac catheterization as having at least 70% stenosis of one major coronary artery were assigned to the case group (n = 184). Healthy individuals with normal blood biochemical values were assigned to the control group (n = 516). MTHFR 677C->T gene polymorphism, lipid profiles, plasma homocysteine and B-vitamins concentrations were measured. Forty-six CAD patients were randomly assigned to one of two groups: a placebo group (n = 22) and a folic acid group (400ug/d folate; n = 24). Intervention was administered for 2 months (8 weeks). The results showed T-allele carriers were positively associated with blood pressure and plasma homocysteine concentration when compared to subjects with 677CC genotype. Plasma homocysteine (>= 12.5 umol/L) (OR, 3.490; 95% CI, 1.233 – 9.877) had a significant association with increased risk of CAD. However, MTHFR 677C->T genotypes had no effect on the risk of CAD. In addition, subjects with plasma PLP < 30 nmol/L exhibited higher blood lipid status and significantly increased risk of CAD (OR, 1.85; 95% CI, 1.16 – 2.95) or risk of hypertension (OR, 16.44, P < 0.001) than subjects with plasma PLP (>= 30 nmol/L. After 8 weeks of supplementation, folic acid supplements did not significantly lower fasting plasma homocysteine concentration. However, 400ug folic acid significantly reduced homocysteine by 1.8 umol/L at week 8 for those subjects with hyperhomocysteinemia, especially for subjects with the T-mutation genotype. In conclusion, T-allele carriers and low PLP (< 30 nmol/L) increased plasma homocysteine concentration, lipid profiles and blood pressure; and plasma homocysteine is associated with the risk of CAD. In addition, a low-dose folic acid supplementation (400 ug/d) may have a significant lowering effect on plasma homocysteine concentration in hyperhomocysteinemic CAD patients.

並列關鍵字

Methylenetetrahydrofolate reductase ； Folate ； Vitamin B-6 ； Folic acid supplements ； Hyperhomocysteinemia ； Hyperlipidemia ； Hypertension ； Coronary artery disease

參考文獻

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