Oliveira I O, Silva L P, Borges M C, Cruz O M, Tessmann J W, Motta J V S, Seixas F K, Horta B L, Gigante D P
Physiology and Pharmacology Department, Universidade Federal de Pelotas, Campus Universitário, Campus Universitário s/n, Pelotas, RS, Brazil.
Post-Graduate Programme in Biothecnology, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, Brazil.
Eur J Clin Nutr. 2017 Feb;71(2):259-266. doi: 10.1038/ejcn.2016.193. Epub 2016 Oct 19.
BACKGROUND/OBJECTIVES: Homocysteine (Hcy) is a key intermediate in methionine metabolism. A high plasma concentration of Hcy is an independent risk factor for cardiovascular diseases among other determinants. In this study, we aimed to investigate the interactions between methylenetetrahydrofolate reductase enzyme gene (MTHFR) polymorphisms and lifestyle variables (smoking, alcohol intake and physical activity) on Hcy concentrations in a young Brazilian population.
SUBJECTS/METHODS: The study population comprised 3803 individuals from the Pelotas Birth Cohort, aged 22-23 years. Allelic discrimination assays and chemiluminescence immunoassays were performed for genotyping and serum Hcy measurements, respectively. Linear regression models were used to explore the effect of gene-lifestyle interactions on Hcy concentrations.
Men carrying the MTHFR 677TT genotype, who were also smokers and drinkers (⩾15 g of alcohol per day), had the highest concentration of Hcy (P-value for the interaction <0.001 for smoking and 0.002 for alcohol intake). In contrast, high folate concentrations attenuated the effects of the MTHFR C677T genotype on serum Hcy concentrations (P-value for interaction <0.001). Also, among males, blood folate concentration was the only lifestyle variable able to modify the influence of MTHFR A1298C genotypes on Hcy concentrations (P-value for the interaction <0.001). There was no strong evidence of an interaction between the MTHFR genotypes and the lifestyle variables in women.
In summary, our study demonstrates a sex difference in Hcy concentrations among Brazilian young adults regarding MTHFR C677T-lifestyle interactions that are worsened under conditions of low blood folate. Identification of potentially modifiable factors related to an increase in homocysteine in young adults, especially in those who are genetically susceptible, is important to prevent negative health consequences in the future.
背景/目的：同型半胱氨酸（Hcy）是甲硫氨酸代谢的关键中间体。高血浆Hcy浓度是心血管疾病的独立危险因素，其他决定因素也是如此。在本研究中，我们旨在调查亚甲基四氢叶酸还原酶基因（MTHFR）多态性与生活方式变量（吸烟、饮酒和体育活动）对巴西年轻人群Hcy浓度的相互作用。
受试者/方法：研究人群包括来自佩洛塔斯出生队列的3803名个体，年龄在22 - 23岁之间。分别进行等位基因鉴别分析和化学发光免疫分析以进行基因分型和血清Hcy测量。使用线性回归模型来探讨基因 - 生活方式相互作用对Hcy浓度的影响。
携带MTHFR 677TT基因型的男性，同时也是吸烟者和饮酒者（每天饮酒⩾15克），其Hcy浓度最高（吸烟的相互作用P值<0.001，饮酒的相互作用P值<0.002）。相反，高叶酸浓度减弱了MTHFR C677T基因型对血清Hcy浓度的影响（相互作用P值<0.001）。此外，在男性中，血叶酸浓度是唯一能够改变MTHFR A1298C基因型对Hcy浓度影响的生活方式变量（相互作用P值<0.001）。没有强有力的证据表明MTHFR基因型与女性生活方式变量之间存在相互作用。
总之，我们的研究表明，在巴西年轻人中，关于MTHFR C677T - 生活方式相互作用，Hcy浓度存在性别差异，在低血叶酸条件下这种差异会加剧。识别与年轻人同型半胱氨酸增加相关的潜在可改变因素，特别是那些基因易感性高的人，对于预防未来的负面健康后果很重要。
