School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.
BMC Med Genet. 2010 Feb 1;11:18. doi: 10.1186/1471-2350-11-18.
Genetic variation in folate metabolism has been associated with survival in utero, the success of in vitro fertilisation, multiple pathologies and longevity.
We have looked at the prevalence of genetic variants of the enzymes MTHFR and TYMS in 2,898 DNA samples derived from five cohorts collected in the United Kingdom. The simultaneous analysis of genetic variants of the MTHFR and TYMS loci was carried out to investigate a putative gene-gene interaction that was first observed in an elderly male population from Norfolk.
We have made a consistent observation in five population cohorts; the proportion of individuals who are homozygous for the 2R allele of the 5'UTR TYMS polymorphism is less in individuals who are homozygous for the T allele of MTHFR 677 than in individuals homozygous for the C allele of MTHFR 677 (p = 0.02).
These data may suggest a gene-gene interaction and could be evidence of genetic selection, with some pregnancies more or less viable as a consequence of genetic variation. If these genetic phenomena affect the way folate is handled at the cellular level in utero it is possible that maternal folic acid intake may over-ride such genetic selection.
叶酸代谢中的遗传变异与宫内生存、体外受精的成功、多种病理学和长寿有关。
我们研究了来自英国五个队列的 2898 个 DNA 样本中 MTHFR 和 TYMS 酶的遗传变异的流行率。对 MTHFR 和 TYMS 基因座的遗传变异进行了同时分析，以研究在诺福克的老年男性人群中首次观察到的假定的基因-基因相互作用。
我们在五个人群队列中进行了一致的观察；5'UTR TYMS 多态性的 2R 等位基因纯合子在 MTHFR 677 等位基因纯合子为 T 的个体中的比例低于 MTHFR 677 等位基因纯合子为 C 的个体（p = 0.02）。
这些数据可能表明存在基因-基因相互作用，并且可能是遗传选择的证据，由于遗传变异，一些妊娠的存活率或多或少。如果这些遗传现象影响了叶酸在宫内细胞水平的处理方式，那么母体叶酸的摄入可能会超过这种遗传选择。
