叶酸代谢途径中的基因-基因相互作用与圆锥动脉干心脏缺陷风险
Gene-gene interactions in the folate metabolic pathway and the risk of conotruncal heart defects.
作者信息
Lupo Philip J, Goldmuntz Elizabeth, Mitchell Laura E
机构信息
Human Genetics Center, Division of Epidemiology and Disease Control, The University of Texas School of Public Health, 1200 Herman Pressler Drive, Houston, TX 77030, USA.
出版信息
J Biomed Biotechnol. 2010;2010:630940. doi: 10.1155/2010/630940. Epub 2010 Jan 12.
Abstract
Conotruncal and related heart defects (CTRD) are common, complex malformations. Although there are few established risk factors, there is evidence that genetic variation in the folate metabolic pathway influences CTRD risk. This study was undertaken to assess the association between inherited (i.e., case) and maternal gene-gene interactions in this pathway and the risk of CTRD. Case-parent triads (n = 727), ascertained from the Children's Hospital of Philadelphia, were genotyped for ten functional variants of nine folate metabolic genes. Analyses of inherited genotypes were consistent with the previously reported association between MTHFR A1298C and CTRD (adjusted P = .02), but provided no evidence that CTRD was associated with inherited gene-gene interactions. Analyses of the maternal genotypes provided evidence of a MTHFR C677T/CBS 844ins68 interaction and CTRD risk (unadjusted P = .02). This association is consistent with the effects of this genotype combination on folate-homocysteine biochemistry but remains to be confirmed in independent study populations.
摘要
圆锥动脉干及相关心脏缺陷（CTRD）是常见的复杂畸形。尽管已确定的风险因素较少，但有证据表明叶酸代谢途径中的基因变异会影响CTRD风险。本研究旨在评估该途径中遗传（即病例）和母体基因-基因相互作用与CTRD风险之间的关联。从费城儿童医院确定的病例-父母三联体（n = 727）对9个叶酸代谢基因的10个功能变体进行了基因分型。对遗传基因型的分析与先前报道的MTHFR A1298C与CTRD之间的关联一致（校正P = 0.02），但没有证据表明CTRD与遗传基因-基因相互作用有关。对母体基因型的分析提供了MTHFR C677T/CBS 844ins68相互作用与CTRD风险的证据（未校正P = 0.02）。这种关联与该基因型组合对叶酸-同型半胱氨酸生物化学的影响一致，但仍有待在独立研究人群中得到证实。
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