台南地區冠狀動脈患者5，10 ──次甲基四氫葉酸酶基因型之檢測   全文下載

Genotyping 5,10-Methylenetetrahydrofolate Reductase for Patients with Coronary Artery Disease in Southern Taiwan

Hyperhomocysteinaemia（高半胱胺酸血症）被證實為腦血管、心血管、冠狀動脈等疾病之危險因子之一。最近有研究指出Homozygous變異的5，10──次甲基四氫葉酸還原?（5,10-Methylenetetrahydrofolate reductase, MTHFR），會使血液中homocysteine濃度提高，所以MTHFR的突變可能是心血管疾病的重要危險因子。本研究之目的即為利用PCR和限制內切?片段長度多型性（RFLP）來篩檢大台南地區心血管疾病患者及正常者之MTHFR基因型，我們發現在54名冠狀動脈病患中MTHFR 677C→T的homozygous變異（MTHFR677-／-）佔11.1%，而在55名正常受檢者為3.6% （P = 0.275）。至於MTHFR1298基因型之檢測方面，結果顯示冠狀動脈病患在MTHFR1298-／-僅有2 位（3.7%），與正常者之比率5.5%差異不大（p = 1.000）。以上結果顯示MTHFR677-／-可能為國人冠狀動脈病變的遺傳因素之一，但MTHFR1298A→C的變異則與國人冠狀動脈病變並無關聯。此外由於在冠狀動脈病患中MTHFR677-／- 僅佔11.1%，而MTHFR1298-／-僅佔3.7%，顯示南台灣地區的冠狀動脈病變並非單由MTHFR677及MTHFR1298基因變異所造成；此與大部分文獻所敘，相去不遠。將來我們將進一步檢測血清中homocysteine、葉酸及維生素B12之含量，以期了解台灣地區MTHFR變異分佈及與血管疾病之關聯性。"

Hyperhomocysteinaemia has been identified as a risk factor for cerebrovascular, peripheral vascular and coronary heart disease (CAD). Individuals with homozygous MTHFR (5,10-Methylenetetrahydrofolate reductase) mutation have significantly elevated plasma homocysteine levels. Two common mutations in MTHFR (MTHFR 677CT and MTHFR 1298AC) may represent an important genetic risk factor in vascular disease. The aim of this research was to investigate these two point mutations of MTHFR for CAD patients and non-CAD controls in Southern Taiwan by PCR-restriction fragment length polymorphism assay. We found that the distribution of the homozygous mutation for MTHFR677 was higher in 54 CAD patients than in 55 non-CAD subjects (11.1% versus 3.6%, P = 0.275). On the other hand, the frequency of MTHFR 1298CC in CAD patients was similar to that of control subjects (P = 1.000). This may suggest there is a trend toward an increased risk of coronary heart disease for individuals that have a 677TT genotype in the Taiwanese population. Finally, the frequency of homozygosity for the two MTHFR common mutations was still low in CAD cases. There may not be an appreciable association of MTHFR mutation to cardiovascular disease in Taiwan. Perhaps a further study including assessment of plasma concentrations of homocysteine, folate and vitamin B12 would be needed to better clarify the relationship between MTHFR polymorphisms and the occurrence of vascular disease. Hyperhomocysteinaemia（高半胱胺酸血症）被證實為腦血管、心血管、冠狀動脈等疾病之危險因子之一。最近有研究指出Homozygous變異的5，10──次甲基四氫葉酸還原酶（5,10-Methylenetetrahydrofolate reductase, MTHFR），會使血液中homocysteine濃度提高，所以MTHFR的突變可能是心血管疾病的重要危險因子。本研究之目的即為利用PCR和限制內切酶片段長度多型性（RFLP）來篩檢大台南地區心血管疾病患者及正常者之MTHFR基因型，我們發現在54名冠狀動脈病患中MTHFR 677C→T的homozygous變異（MTHFR677-／-）佔11.1%，而在55名正常受檢者為3.6% （P = 0.275）。至於MTHFR1298基因型之檢測方面，結果顯示冠狀動脈病患在MTHFR1298-／-僅有2 位（3.7%），與正常者之比率5.5%差異不大（p = 1.000）。以上結果顯示MTHFR677-／-可能為國人冠狀動脈病變的遺傳因素之一，但MTHFR1298A→C的變異則與國人冠狀動脈病變並無關聯。此外由於在冠狀動脈病患中MTHFR677-／- 僅佔11.1%，而MTHFR1298-／-僅佔3.7%，顯示南台灣地區的冠狀動脈病變並非單由MTHFR677及MTHFR1298基因變異所造成；此與大部分文獻所敘，相去不遠。將來我們將進一步檢測血清中homocysteine、葉酸及維生素B12之含量，以期了解台灣地區MTHFR變異分佈及與血管疾病之關聯性。