叶酸代谢相关基因假定功能性单核苷酸多态性与脊柱裂的遗传关联研究
Genetic association study of putative functional single nucleotide polymorphisms of genes in folate metabolism and spina bifida.
作者信息
Martinez Carla A, Northrup Hope, Lin Jone-Ing, Morrison Alanna C, Fletcher Jack M, Tyerman Gayle H, Au Kit Sing
机构信息
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center, Houston, TX, USA.
出版信息
Am J Obstet Gynecol. 2009 Oct;201(4):394.e1-11. doi: 10.1016/j.ajog.2009.06.042. Epub 2009 Aug 15.
Abstract
OBJECTIVE
We tested putative functional single nucleotide polymorphisms (SNPs) in genes that regulate the folate/homocysteine metabolism pathway for their contribution to spina bifida (SB) susceptibility.
STUDY DESIGN
The study consisted of 610 unrelated simplex SB patient families. Genotypes of 46 SNPs located in the coding sequence or promoter region of 11 genes were investigated. Associations between transmission of alleles and SB in the offspring were examined using the reconstruction combined transmission disequilibrium test.
RESULTS
Significant association of SNP rs5742905 in cystathionine-beta-synthase, rs1643649 in dihydrofolate reductase, rs2853533 in thymidylate synthetase, and rs3737965 in methylenetetrahydrofolate reductase was found (P = .015, .041, .021, and .007 respectively).
CONCLUSION
Transmission disequilibrium of SNP alleles in cystathionine-beta-synthase, dihydrofolate reductase, methylenetetrahydrofolate reductase, and thymidylate synthetase confers an increased susceptibility to SB.
摘要
目的
我们检测了叶酸/同型半胱氨酸代谢途径调控基因中的推定功能性单核苷酸多态性（SNP），以评估其对脊柱裂（SB）易感性的影响。
研究设计
该研究包括610个无亲缘关系的单纯性SB患者家庭。对位于11个基因编码序列或启动子区域的46个SNP的基因型进行了研究。使用重建联合传递不平衡检验来检查等位基因传递与后代SB之间的关联。
结果
发现胱硫醚-β-合酶中的SNP rs5742905、二氢叶酸还原酶中的rs1643649、胸苷酸合成酶中的rs2853533以及亚甲基四氢叶酸还原酶中的rs3737965存在显著关联（P值分别为0.015、0.041、0.021和0.007）。
结论
胱硫醚-β-合酶、二氢叶酸还原酶、亚甲基四氢叶酸还原酶和胸苷酸合成酶中SNP等位基因的传递不平衡会增加患SB的易感性。
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