Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration
Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration
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DOI：
10.1111/j.1399-0004.2004.00250.x
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发表时间：
2004-06-01
影响因子：
3.5
通讯作者：
Hegele, RA
中科院分区：
文献类型：
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作者：
Wang, J;Huff, AM;Hegele, RA
血浆总同型半胱氨酸(THcy)浓度是动脉粥样硬化的独立危险因素，有许多遗传和环境决定因素。虽然编码亚甲基四氢叶酸还原酶的亚甲基四氢叶酸还原酶亚甲基四氢叶酸还原酶的耐热多态是与血浆tHCy变异相关的最好的遗传因素，但其他候选基因正在评估中。最近，我们发现胱硫氰尿症是由编码胱硫氨酸伽马裂解酶的Cth基因突变引起的，该酶在反式硫化途径中将胱硫氨酸转化为半胱氨酸。我们还在Cth基因第12外显子发现了一个常见的单核苷酸多态(SNP)，即c.1364G>；T(S403I)。在目前的分析中，我们在496名高加索受试者中研究了该SNP的基因型与血浆tHcy浓度的关系。CTH 1364T/T纯合子的平均血浆tHcy浓度显著高于其他基因型的受试者，且CTH和MTHFR的效应大小相似。研究结果表明，Cth的共同变异可能是血浆tHcy浓度的决定因素。
Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best-studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine gamma-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations.