Genetic and environmental influences on plasma homocysteine: Results from a Danish twin study
Genetic and environmental influences on plasma homocysteine: Results from a Danish twin study
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DOI：
10.1373/clinchem.2006.082149
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发表时间：
2007-05-01
影响因子：
9.3
通讯作者：
Kyvik, Kirsten O.
中科院分区：
文献类型：
--
作者：
Bathum, Lise;Petersen, Inge;Kyvik, Kirsten O.
背景：血浆同型半胱氨酸升高与许多临床疾病有关，包括动脉粥样硬化和缺血性中风。我们评估了遗传和环境对成年双胞胎同型半胱氨酸的影响，并测试了3种候选多态性的影响。方法：对1206例健康双胞胎进行同型半胱氨酸分析，对3个多态性进行基因分型：MTHFR 677C > T、MTR 2756A >g和NNMT （dbSNP: rs694539）。为了对MTHFR基因座进行数量性状连锁分析，在MTHFR基因座的每个位点上添加2个定位的遗传标记进行基因分型。使用生物特征结构方程模型对双胞胎数据进行分析，并对两个年龄队列进行联合关联和连锁分析。结果：年龄、性别和MTHFR基因型对同型半胱氨酸浓度有显著影响，而其他基因型与同型半胱氨酸浓度无关。同型半胱氨酸的变异可以完全归因于加性遗传因素和非共享环境因素，估计18-39岁总变异的加性遗传比例为0.63 (95% CI, 0.53-0.71)， 40-65岁的加性遗传比例为0.27 （95% CI, 0.10-0.41）。据估计，MTHFR位点的影响解释了18-39岁人群中总表型变异的53% （95% CI, 0.07-0.67）和40-65岁人群中总表型变异的24% (95% CI, 0.00-0.39)，即几乎所有的加性遗传变异。结论：同型半胱氨酸浓度具有高遗传性，随年龄增长而降低。MTHFR基因位点几乎负责所有可归因于遗传因素的变异，其他遗传变异的影响很小。(c) 2007美国临床化学协会。
Background: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms.Methods: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C > T, MTR 2756A > G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts.Results: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and non-shared environmental factors, with an estimated additive genetic proportion of total variation at age 18-39 years of 0.63 (95% CI, 0.53-0.71) and at age 40-65 years of 0.27 (95% CI, 0.10-0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07-0.67) of the total phenotypic variation in persons 18-39 years old and 24% (95% CI, 0.00-0.39) in persons 40-65 years old, i.e., almost all additive genetic variance.Conclusions: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations. (c) 2007 American Association for Clinical Chemistry.