Gemmati D, Serino M L, Trivellato C, Fiorini S, Scapoli G L
Center for the Study of Hemostasis and Thrombosis, University of Ferrara, c.so Giovecca 203, 44100 Ferrara, Italy.
Haematologica. 1999 Sep;84(9):824-8.
Hyperhomocysteinemia, due to a combination of genetic and environmental factors, is considered to be a risk factor for vascular disease. Individuals with the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR), due to homozygous C677T MTHFR gene mutation, have significantly raised plasma levels of homocysteine and may be at increased risk of vascular disease. However, it is still controversial a direct association between C677T homozygosity and the occurrence of vascular disease is still controversial.
To clarify the contribution of C677T MTHFR mutation in arterial occlusive disease (AOD) or venous thromboembolism (VTE), we performed a case-controlled study including 160 cases with AOD and 180 cases with VTE attending our referral center and compared them with 200 matched healthy controls. MTHFR gene mutation was evaluated by PCR and odds ratios (OR) and the 95% confidence intervals (CI) were used to estimate the risk for venous or arterial thrombosis.
There was a high prevalence of homozygotes for the mutated MTHFR allele among the whole group of cases with arterial disease (OR = 2.35, p = 0.001). Considering the AOD cases with and those without associated risk factors for arterial disease separately the difference remained significant only in the latter group (p = 0.168 and P<0.001 respectively). In contrast, the prevalence of mutated homozygotes among the whole group of cases with VTE was not significantly different from that in the control group (OR = 1.67; p = 0.070). Excluding VTE cases with inherited thrombophilia or with circumstantial risk situations the value increased in both subgroups (OR = 2.26; p = 0.006 and OR = 2.03; p = 0.033 respectively). Considering only VTE cases with neither inherited thrombophilia nor circumstantial risk situations the risk increased further (OR = 2.57; p = 0.017).
These data suggest that in selected patients homozygosity for the MTHFR mutation increases the risk of both arterial and venous thromboses and that differences in selection criteria for the patient group may be responsible in part for the controversial association of the MTHFR mutation and vascular disease.
由于遗传和环境因素的共同作用，高同型半胱氨酸血症被认为是血管疾病的一个危险因素。因纯合子C677T亚甲基四氢叶酸还原酶（MTHFR）基因突变而具有MTHFR热不稳定变异型的个体，其血浆同型半胱氨酸水平显著升高，可能有更高的血管疾病风险。然而，C677T纯合性与血管疾病发生之间的直接关联仍存在争议。
为阐明C677T MTHFR突变在动脉闭塞性疾病（AOD）或静脉血栓栓塞症（VTE）中的作用，我们进行了一项病例对照研究，纳入了在我们转诊中心就诊的160例AOD患者和180例VTE患者，并将他们与200例匹配的健康对照进行比较。通过聚合酶链反应（PCR）评估MTHFR基因突变情况，并用优势比（OR）和95%置信区间（CI）来估计静脉或动脉血栓形成的风险。
在整个动脉疾病病例组中，突变的MTHFR等位基因纯合子的患病率较高（OR = 2.35，p = 0.001）。分别考虑有和没有动脉疾病相关危险因素的AOD病例，差异仅在后者组中仍然显著（分别为p = 0.168和P<0.001）。相比之下，整个VTE病例组中突变纯合子的患病率与对照组没有显著差异（OR = 1.67；p = 0.070）。排除有遗传性血栓形成倾向或有间接风险情况的VTE病例后，两个亚组的该值均升高（分别为OR = 2.26；p = 0.006和OR = 2.03；p = 0.033）。仅考虑既没有遗传性血栓形成倾向也没有间接风险情况的VTE病例，风险进一步增加（OR = 2.57；p = 0.017）。
这些数据表明，在特定患者中，MTHFR突变纯合性会增加动脉和静脉血栓形成的风险，并且患者组选择标准的差异可能部分导致了MTHFR突变与血管疾病之间存在争议的关联。
