Strauss Ewa, Waliszewski Krzysztof, Gabriel Marcin, Zapalski Stanisław, Pawlak Andrzej L
Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszyńska 32, 60-479 Poznań, Poland.
J Appl Genet. 2003;44(1):85-93.
Abdominal aortic aneurysm (AAA) presents itself as a progressive dilation of the abdominal aorta, leading--if untreated--to rupture. It is a common disease of the elderly, with a complex etiology. Several genetic, biochemical and environmental factors are recognized as relevant for the pathogenesis of AAA. We determined the polymorphism of the MTHFR (methylenetetrahydrofolate reductase) gene within the fourth exon (C677T) in 63 patients with AAA and compared it to that in 75 subjects of the population sample. The frequencies of the C/C, C/T and T/T genotypes were 65%, 27%, and 8% in the population sample and 33%, 60%, and 6% in the patients. This corresponds to a 4.4-fold greater risk of AAA in subjects who have the 677C/T variant of MTHFR, as compared with those who are 677C/C (p < 0.0001; 95% CI=2.11-9.34). The frequency of allele MTHFR 677T in patients (0.37) was higher than in the population sample (0.21; p < 0.007). This association between the common allele of the MTHFR gene--MTHFR 677T--and the development of AAA suggests that elevated homocysteine (Hcy) may disturb the function of the aortic wall. The disturbance may involve enhancement of elastin degradation, the process enhanced by mild hyperhomocysteinemia in minipigs. The magnitude of this effect, which refers to the AAA patients unselected for familial occurrence, indicates that the disturbance of aortic wall physiology caused by the presence of the MTHFR 677T allele is greater than the effect of the earlier described allele disequilibrium at the polymorphic alleles of the PAI1 (plasminogen activator inhibitor 1) gene seen only in familial cases of AAA.
腹主动脉瘤（AAA）表现为腹主动脉的进行性扩张，若不治疗会导致破裂。它是一种常见的老年疾病，病因复杂。几种遗传、生化和环境因素被认为与AAA的发病机制相关。我们测定了63例AAA患者第四外显子（C677T）内亚甲基四氢叶酸还原酶（MTHFR）基因的多态性，并将其与75名人群样本受试者的多态性进行比较。在人群样本中，C/C、C/T和T/T基因型的频率分别为65%、27%和8%，在患者中分别为33%、60%和6%。这表明，与MTHFR 677C/C的受试者相比，具有MTHFR 677C/T变异的受试者患AAA的风险高4.4倍（p<0.0001；95%CI=2.11 - 9.34）。患者中MTHFR 677T等位基因的频率（0.37）高于人群样本（0.21；p<0.007）。MTHFR基因的常见等位基因——MTHFR 677T——与AAA发生之间的这种关联表明，高同型半胱氨酸（Hcy）水平可能会干扰主动脉壁的功能。这种干扰可能涉及弹力蛋白降解的增强，小型猪的轻度高同型半胱氨酸血症会加剧这一过程。这种效应的程度（针对未按家族发病情况进行选择的AAA患者）表明，MTHFR 677T等位基因的存在对主动脉壁生理功能的干扰大于仅在AAA家族病例中出现的纤溶酶原激活物抑制剂1（PAI1）基因多态性等位基因的早期描述的等位基因失衡效应。
