Botto Nicoletta, Andreassi Maria Grazia, Manfredi Samantha, Masetti Serena, Cocci Franca, Colombo Maria Giovanna, Storti Simona, Rizza Antonio, Biagini Andrea
CNR, Institute of Clinical Physiology, G Pasquinucci Hospital, via Aurelia Sud-Montepepe, 54100 Massa, Italy.
Eur J Hum Genet. 2003 Sep;11(9):671-8. doi: 10.1038/sj.ejhg.5201024.
Epidemiological studies indicated a role for polymorphisms in genes of folate and homocysteine (Hcy) metabolism in the etiology of neurodegenerative disease, congenital defects and coronary artery disease (CAD). This study investigated the effect of several polymorphisms [C677 T, A1298C of methylenetetrahydrofolate reductase (MTHFR) and A66G of methionine synthase reductase (MTRR) genes] on Hcy levels and DNA damage in 68 patients who underwent coronary angiography. Plasma Hcy concentrations were higher in patients with multivessel disease with respect to monovessel disease and no-CAD patients (19.4+/-2.6 vs 11.6+/-1.2 and 13.7+/-1.4 micromol/l, respectively; P=0.03). 677TT patients had higher Hcy levels than those with 677CC or 677CT genotypes (26.2+/-4.3 vs 13.1+/-1.4 and 13.0+/-1.4 micromol/l, respectively; P=0.0006). No significant associations were found between A1298C and A66G polymorphisms and plasma Hcy levels. Among patients with 677CC genotype, 66GG individuals tended to have higher levels of Hcy than 66AA homozygotes (14.5+/-1.9 vs 8.9+/-0.7 micromol/l, P=0.06). Multivessel disease patients showed an increased frequency of DNA damage, measured by the micronucleus (MN) frequency, as compared to monovessel disease and no-CAD subjects (12.5+/-1.1 vs 8.5+/-0.8 and 8.2+/-0.9, respectively; P=0.006). The MN were positively correlated with Hcy levels (r=0.33, P=0.006) and were significantly higher in subjects with the 677TT genotype compared with the 677CC or 677CT genotypes (14.4+/-2.0 vs 8.8+/-1.2 and 9.5+/-0.7, respectively; P=0.006). A1298C and A66G polymorphisms had no effect on MN frequency. However, among 677TT patients, 66GG subjects tended to have higher levels of MN than those 66AG and 66AA (18.2+/-3.6 vs 13.8+/-4.0 and 10.3+/-1.7, respectively; P=NS). Our results indicate that genetic instability may be associated with increased risk for multiple Hcy-related diseases.
流行病学研究表明，叶酸和同型半胱氨酸（Hcy）代谢相关基因的多态性在神经退行性疾病、先天性缺陷和冠状动脉疾病（CAD）的病因学中发挥作用。本研究调查了几种多态性[亚甲基四氢叶酸还原酶（MTHFR）的C677T、A1298C以及甲硫氨酸合成酶还原酶（MTRR）基因的A66G]对68例行冠状动脉造影患者的Hcy水平和DNA损伤的影响。多支血管病变患者的血浆Hcy浓度高于单支血管病变患者和无CAD患者（分别为19.4±2.6 vs 11.6±1.2和13.7±1.4 μmol/L；P=0.03）。677TT基因型患者的Hcy水平高于677CC或677CT基因型患者（分别为26.2±4.3 vs 13.1±1.4和13.0±1.4 μmol/L；P=0.0006）。未发现A1298C和A66G多态性与血浆Hcy水平之间存在显著关联。在677CC基因型患者中，66GG个体的Hcy水平往往高于66AA纯合子（14.5±1.9 vs 8.9±0.7 μmol/L，P=0.06）。与单支血管病变和无CAD受试者相比，多支血管病变患者的DNA损伤频率（通过微核（MN）频率测量）增加（分别为12.5±1.1 vs 8.5±0.8和8.2±0.9；P=0.006）。MN与Hcy水平呈正相关（r=0.33，P=0.006），677TT基因型受试者的MN显著高于677CC或677CT基因型受试者（分别为14.4±2.0 vs 8.8±1.2和9.5±0.7；P=0.006）。A1298C和A66G多态性对MN频率无影响。然而，在677TT患者中，66GG受试者的MN水平往往高于66AG和66AA受试者（分别为18.2±3.6 vs 13.8±4.0和10.3±1.7；P=无统计学意义）。我们的结果表明，基因不稳定性可能与多种Hcy相关疾病的风险增加有关。
