LTA 804C/A基因变异与冠心病易感性、严重度和分子标志物之间的关系

Association between genetic variation of lymphotoxin-α 804C/A and susceptibility,lesion severity and molecular makers of coronary heart disease

目的研究淋巴毒素-α(LTA)804C/A基因变异与冠心病(CHD)易感性、病变严重度和分子标志物之间的关系。方法用聚合酶链反应-序列特异性扩增技术(PCR-SSP)对184例CHD患者和118例对照组(CTL)分别检测LTA 804位点基因型、等位基因及其分布频率;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法和散射比浊法测试血浆LTA、血管细胞黏附分子-1(VCAM-1)和C-反应蛋白(CRP)水平;分析LTA基因变异与CHD易感风险、DVN、SSI、血浆LTA、CRP、VCAM-1水平之间的关系。结果LTA 804C/A变异与CHD患病风险显著关联(AA+CA基因型OR=1.47,A等位基因OR=1.54,均P<0.05),AA基因型和A等位基因的频率在CHD组比CTL组显著增高(均P<0.01);804位点变异型(AA+CA)比野生型(CC)的DVN、SSI、VCAM-1及CRP显著增高(P均<0.05);但血浆LTA无显著变化。结论LTA 804C→A基因变异可能是CHD患病的易感基因型,且与冠状动脉病变程度和炎性细胞因子过度表达有关,但与LTA转录无关。

Objective To investigate association between genetic variation of lymphotoxin-α （LTA） 804C/A and susceptibility, lesion severity and molecular makers of coronary hcart disease （CHD）. Methods Sequence specific primers-polymerase chain reaction （PCR-SSP） was used for the detection of genotypes and alleles in LTA 804 locus in 184 CHD patients and 118 controls. Diseased vessel numbers （DVN） and stenotic severity integral （SSI） by coronary angiography and serum levels of LTA, vascular cell adhesion molecule-1 （VCAM-1） and C-reactive protein （CRP） were measured by enzyme -linked immunosorbent assay （ELISA） and nephelometry. Association between I.TA gene variants and CHD risk, DVN,SSI as well as plasma levels of I.TA, VCAM-1 and CRP were analyzed. Results LTA 804 C/A variant was significantly associated with CHD （OR= 1.47 in genotype AA＋ CA, OR= 1.54 in A allele, all P〈0.05）. Frequency of AA genotype and A allele in CHD group was significantly higher compared to control group （both P〈20.01）. Patients with （AA＋CA） genotype had significantly higher DVN, SSI, CRP and VCAM-1 levels than wild type （CC）,but there was no significant difference of plasma LTA level between AA-CA genotype and CC genotype. Conclusions I.TA 804C/A variant may be a genetic predictor of CHD. It is associated with severity of coronary lesion and over-expression of inflammatory cytokines, but not associated with transcriptional level of LTA .