Husemoen Lise Lotte N, Thomsen Troels F, Fenger Mogens, Jørgensen Henrik L, Jørgensen Torben
Research Centre for Prevention and Health, Copenhagen County, Glostrup University Hospital, Glostrup, Denmark.
Genet Epidemiol. 2003 May;24(4):322-30. doi: 10.1002/gepi.10239.
Elevation in plasma total homocysteine (tHcy) is believed to be causally related to cardiovascular disease. Like age and sex, the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR(C677T)) is an important nonmodifiable determinant of tHcy, which may be considered when describing normal ranges of tHcy in the general population. We investigated the simultaneous effect of sex, age, and MTHFR(C677T) genotype on the distribution of tHcy in a cross-sectional study design. THcy concentrations and MTHFR(C677T) genotype were determined in a population-based sample of 2,788 Danish men and women aged 30-60 years participating in the Inter99 Study. The prevalences of MTHFR(C677T) genotypes were 48.8% (CC), 42.4% (CT), and 8.8% (TT). The overall median tHcy was 8.1 micromol/l, and the 2.5-97.5 percentiles were 4.8-17.8 micro mol/l. The estimated proportionally higher level of tHcy in men compared to women was 14.3% (P<0.001). A significant interaction term was found between age and MTHFR(C677T) genotype (P<0.001). The estimated changes in tHcy per 5 years of age were 1.5% in CC individuals (P<0.01), 2.1% in CT individuals (P<0.001), and -4.1% in TT individuals (P<0.01). The T allele was associated with elevated tHcy. However, the proportionally higher level of tHcy in TT individuals compared to CT and CC individuals decreased with increasing age. The MTHFR(C677T) polymorphism explained 6% of the phenotypic variation in tHcy. In conclusion, we found that tHcy is associated with sex, age, and MTHFR genotype. Our results indicate that the effect of age is modified by MTHFR genotype.
血浆总同型半胱氨酸（tHcy）升高被认为与心血管疾病存在因果关系。与年龄和性别一样，亚甲基四氢叶酸还原酶（MTHFR(C677T)）的热不稳定变体是tHcy的一个重要不可改变的决定因素，在描述普通人群tHcy的正常范围时可能需要考虑这一因素。我们在一项横断面研究设计中，研究了性别、年龄和MTHFR(C677T)基因型对tHcy分布的同时影响。在参与Inter99研究的2788名30至60岁丹麦男性和女性的基于人群的样本中，测定了tHcy浓度和MTHFR(C677T)基因型。MTHFR(C677T)基因型的患病率分别为48.8%（CC）、42.4%（CT）和8.8%（TT）。总体tHcy中位数为8.1微摩尔/升，2.5 - 97.5百分位数为4.8 - 17.8微摩尔/升。男性tHcy水平估计比女性高14.3%（P<0.001）。发现年龄与MTHFR(C677T)基因型之间存在显著的交互作用项（P<0.001）。每增加5岁，CC个体的tHcy估计变化为1.5%（P<0.01），CT个体为2.1%（P<0.001），TT个体为 - 4.1%（P<0.01）。T等位基因与tHcy升高有关。然而，TT个体相对于CT和CC个体的tHcy较高比例随着年龄增长而降低。MTHFR(C677T)多态性解释了tHcy表型变异的6%。总之，我们发现tHcy与性别、年龄和MTHFR基因型有关。我们的结果表明，年龄的影响因MTHFR基因型而改变。
