Pereira Alexandre C, Schettert Isolmar Tadeu, Morandini Filho Antônio Alberto F, Guerra-Shinohara Elvira Maria, Krieger José E
Laboratorio de Genética e Cardiologia Molecular, InCor-Instituto do Coracao-HCFMUSP, Av. Dr. Eneas de Carvalho Aguiar 44, SP 05403-000, Sao Paulo, Brazil.
Clin Chim Acta. 2004 Feb;340(1-2):99-105. doi: 10.1016/j.cccn.2003.09.016.
A large body of evidence links plasma concentrations of homocysteine and cardiovascular disease. Several genetic and environmental variables may modulate such relationship. We investigated the influence of methylenetetrahydrofolate reductase (MTHFR) gene variants C677T, A1298C, and T1317C on homocysteine, folate, and cobalamin concentrations in a sample of individuals from a mild folate deficiency population to better clarify the complex interactions existing among these variables.
In the present study, 209 individuals belonging to an admixed urban population characterized by mild folate deficiency were investigated. MTHFR gene variants C677T, A1298C, and T1317C were genotyped and homocysteine-, folate-, and cobalamin-determined for each individual.
Univariate analyses showed a significant association between the C677T variant with homocysteine (P<0.001) and cobalamin (P=0.005) as well as a significant relationship between the T allele and serum folate concentrations (P<0.05). The TT genotype of the C677T polymorphism remained significantly associated with log-transformed homocysteine even after adjustment for age, sex, smoking status, ethnicity, folate, and cobalamin concentrations (P<0.01). Both univariate and multivariate analysis have failed to show any effect of the A1298C and T1317C genetic variants in homocysteine concentrations in this population. Finally, a significant interaction between folate and C677T polymorphism in the determination of homocysteine was also disclosed (P<0.005).
Taken together, these results demonstrate a significant interaction between serum folate and MTHFR genotype in predicting homocysteine concentrations. One may consider that a differential response of homocysteine to folic acid supplementation may depend on MTHFR genotype which may have important implications when attempting to lower homocysteine concentrations in populations with mild folate deficiency.
大量证据表明血浆同型半胱氨酸浓度与心血管疾病相关。若干遗传和环境变量可能会调节这种关系。我们研究了亚甲基四氢叶酸还原酶（MTHFR）基因变异C677T、A1298C和T1317C对轻度叶酸缺乏人群样本中同型半胱氨酸、叶酸和钴胺素浓度的影响，以更好地阐明这些变量之间存在的复杂相互作用。
在本研究中，对209名属于以轻度叶酸缺乏为特征的混合城市人群的个体进行了调查。对MTHFR基因变异C677T、A1298C和T1317C进行基因分型，并测定每个个体的同型半胱氨酸、叶酸和钴胺素水平。
单因素分析显示，C677T变异与同型半胱氨酸（P<0.001）和钴胺素（P=0.005）之间存在显著关联，T等位基因与血清叶酸浓度之间也存在显著关系（P<0.05）。即使在对年龄、性别、吸烟状况、种族、叶酸和钴胺素浓度进行校正后，C677T多态性的TT基因型与对数转换后的同型半胱氨酸仍显著相关（P<0.01）。单因素和多因素分析均未显示A1298C和T1317C基因变异对该人群同型半胱氨酸浓度有任何影响。最后，还揭示了叶酸与C677T多态性在同型半胱氨酸测定中的显著相互作用（P<0.00
