淋巴毒素-α/半乳糖凝集素-2基因变异与冠心病风险及分子标志物之间关系

Association between Genetic Variation of Lymphotoxin-α/LGALS2 and Risk of Coronary Arteriosclerosis Disease and Molecule Makers

目的:研究淋巴毒素-α(LTA)804C/A及其配体半乳糖凝集素-2(LGALS2)C3279T基因变异与冠心病(CAD)罹患风险之间的关系。方法:用聚合酶链反应-序列特异性扩增技术(PCR-SSP)和聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)分别检测284例CAD患者和218例对照组LTA804位点及LGALS23279位点基因型、等位基因和联合单倍型;用冠状动脉造影测试病变血管支数(DVN)和狭窄程度积分(SSI);用ELISA法测试血浆LTA和血管细胞黏附分子-1(VCAM-1)水平;用散射比浊法测量血浆C-反应蛋白(CRP)水平。分析LTA和LGALS2基因变异与CAD发病风险、DVN,SSI、血浆LTA、VCAM-1和CRP水平之间的关系。结果:LTA804C/A和单倍型AACC与CAD发病风险显著关联(OR=1.74,2.64);LGALS2基因型CT+TT、T等位基因和单倍型CCTT发生CAD风险显著降低(OR=0.49,0.58,0.41);LTA804变异型比野生型的DVN,SSI、VCAM-1及CRP显著增高,LGALS2则与此相反。结论:LTA804/LGALS23279基因变异可能是CAD发病的风险/保护基因型,分别对冠脉病变程度和炎性细胞因子过度表达起促进/抵御作用。

Objective：To investigate association between genetic variants of 804 C/A in lymphotoxin-α （LTA）and 3 279C/T in LGALS2 and susceptibility risk of coronary arteriosclerosis disease （CAD）. Methods： Sequence specific primers-polymerase chain reaction （PCR-SSP） and polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was respectively used for the detection of genotypes, alleles and haplotypes of two SNP loci in 284 CAD cases and 218 controls. Diseased vessel numbers （DVN） and stenostic severity integral （SSI） by coronary arteriogram , serum levels of LTA and vascular cell adhesion molecule-1 （VCAM-1） and C-reactive protein （CRP） by enzyme -linked immunosorbent assay （ELISA） and nephelometry were also tested . Associations between gene variants in two SNP loci and CAD risk and Molecule Makers （LTA, CRP and VCAM-1） were analysed. Results： 804C/A variant in LTA and haplotype AACC had significantly higher risk of CAD （OR = 1.74,2.64）but genotype CT ＋ TT and allele T in LGALS2 and haplotype CCTT showed lower risk of CAD than their wildtypes （OR= 0. 49,0. 58,0. 41）. A significantly higher DVN, SSI, CRP and VCAM-1 in LTA 804 locus and inverse changes of those in LGALS2 were found when compared variant genotypes with wildtypes. Conclusion：LTA 804 / LGALS2 3 279 genetic variants may be risk/protection genotypes of CAD attacks and pay a promoting / preventing rule for processing of coronary lesion and excessive expressing of inflammatory cytokine.