Cystathionine β-synthase polymorphisms and hyperhomocysteinaemia:: an association study
Cystathionine β-synthase polymorphisms and hyperhomocysteinaemia:: an association study
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DOI：
10.1038/sj.ejhg.5200899
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发表时间：
2003-01-01
影响因子：
5.2
通讯作者：
Blom, HJ
中科院分区：
文献类型：
--
作者：
Lievers, KJA;Kluijtmans, LAJ;Blom, HJ
高同型半胱氨酸血症通常被认为是动脉闭塞性疾病和静脉血栓形成的独立和分级的危险因素。同型半胱氨酸降解的唯一途径是在转硫途径中转化为半胱氨酸，其中调节步骤由胱硫醚β-合酶（CBS）催化。因此，CBS功能的轻度损害可能影响同型半胱氨酸浓度，特别是蛋氨酸负荷后，并因此影响心血管疾病（CVD）风险。我们分析了CBS基因中的两个沉默多态性和一个短串联重复序列（即699 C-->T，1080 C-->T和-5697（GT）STR）作为与功能多态性潜在连锁不平衡的遗传标记。我们在190例动脉闭塞性疾病患者和381例对照者中评估了它们与空腹和蛋氨酸后负荷同型半胱氨酸的关系。未发现病例组和对照组之间CBS基因型频率存在差异，也未发现特定CBS基因型与动脉闭塞性疾病风险升高相关。虽然我们确实发现了两个单核苷酸多态性和GT STR之间的高连锁不平衡率，但研究的三种CBS变体定义的基因型均未显示与空腹、负荷后升高或甲硫氨酸负荷后同型半胱氨酸浓度升高相关。总之，我们没有发现任何迹象表明CBS基因的遗传变异与同型半胱氨酸浓度增加有关。
Hyperhomocysteinaemia is generally accepted as an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. The only way of homocysteine degradation is conversion to cysteine in the transsulfuration pathway in which the regulating step is catalysed by cystathionine beta-synthase (CBS). Mild impairment of CBS function could therefore affect homocysteine concentration, in particular after methionine loading, and consequently cardiovascular disease (CVD) risk. We analysed two silent polymorphisms and one short tandem repeat in the CBS gene (ie 699C-->T, 1080C-->T and -5697 (GT) STR) as genetic markers potentially in linkage disequilibrium with a functional polymorphism. We assessed their association with fasting and post-methionine load homocysteine in 190 patients with arterial occlusive disease, and in 381 controls. No differences in CBS genotype frequencies between cases and controls were found, nor was a particular CBS genotype associated with an elevated risk of arterial occlusive disease. Although we did find a high rate of linkage disequilibrium between the two single nucleotide polymorphisms and the GT STR, none of the genotypes defined by the three CBS variants studied showed an association with elevated fasting, post-load or increase upon methionine loading homocysteine concentrations. In conclusion, we did not find any indication that genetic variation in the CBS gene is associated with increased homocysteine concentrations.