摘要
目的 探讨纤溶酶原活化剂抑制物 - 1(plasminogen activator inhibitor- 1,PAI- 1)基因和纤维蛋白原β链基因多态性与狼疮性肾炎 (lupus nephritis,L N)肾小球微血栓形成之间的相关性。方法 选取10 1例 L N患者 ,依据肾活检组织肾小球微血栓的有无 ,将患者分为两组 :L N伴血栓 (L N+T)组 46例 ;不伴血栓 (L N- T)组 5 5例。应用聚合酶链反应 -限制性片段长度多态性和聚合酶链反应 -序列长度多态性技术分别分析两候选基因的基因型。正常对照组为 12 8名健康成人。结果 (1) PAI- 1基因 4G/ 4G基因型和4G等位基因与 L N+T组显著相关 ;L N中 4G/ 4G型患者发生肾小球袢内血栓的相对风险率的比值比(odds ratio,OR)为 2 .96 ,95 %可信区间 (confidence interval,CI) :1.2 6～ 6 .92 ;(2 )纤维蛋白原 β链基因G/ A+A/ A基因型和 A型等位基因与 L N+T组显著相关 ;L N中 A型等位基因携带者发生肾小球袢内血栓的相对风险率为 OR=2 .44 ,95 % CI:0 .98～ 5 .5 9;(3) L N患者若同时兼有上述两基因的血栓易感基因型 ,其发生肾小球微血栓的相对风险率明显增加 ,OR=4.5 ,95 % CI:1.34～ 15 .12 ;血栓易感基因型的混合病因分值 (4 5 .98% )也高于各自单独的病因分值 (PAI- 1基因 4G/ 4G型为 31.6 7%、纤维蛋白原
Objective To explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene -675 4G/5G and β fibrinogen gene -455 G/A variations to glomerular microthrombosis (T) in lupus nephritis (LN). Methods One hundred and one patients with biopsy proven LN were divided into two groups according to the presence or absence of glomerular microthrombus, i.e. group LN + T(n=46) and group LN - T(n = 55). The genotypes of PAI-1 gene and β fibrinogen gene were profiled by polymerase chain reaction-sequence length polymorphism (PCR-SLP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. Clinical baseline data at the time of renal biopsy were collected. Normal controls consisted of 128 unrelated healthy adults. The etiologic fractions (EF) were calculated for estimating the contribution of risk genotypes of the two candidate genes to an increase in susceptibility to glomerular microthrombosis in LN patients. Results Both the 4G/4G genotype and the 4G allele of PAI-1 gene occurred more frequently in group LN + T (47.83% and 0. 685) than in group LN - T (23.64% and 0.507)(P<0.05) and normal controls (28.13% and 0.570)(P<0.05). The PAI-1 4G/4G genotype was significantly associated with microthrombosis (OR = 2.96, 95%CI: 1.26 - 6.92). Besides, the prevalence of the genotypes carrying the A allele of β fibrinogen gene, i.e. G/A and A/A, as well as the prevalence of the A allele per se, was increased in group LN + T (47.83% and 0. 261) versus group LN - T (27.27% and 0.145) (P<0.05). LN patients carrying the A allele had a high risk of glomerular thrombosis (OR = 2.44, 95%CI: 0.98 - 5.59). In addition, the presence of the PAI-1 4G/4G genotype together with the A allele of the β fibrinogen gene was found to be a greater risk factor (OR = 4.5,95%CI:1.34 - 15.12) for glomerular thrombosis in LN than the 4 G / 4 G genotype or the A allele alone. The pooled EF (45.98%) for the risk genotypes of both PAI-1 gene and β fibrinogen gene was also higher than that for the risk genotypes of
出处
《中华医学遗传学杂志》
EI
CAS
CSCD
2002年第1期1-5,共5页
Chinese Journal of Medical Genetics
基金
解放军医药卫生杰出中青年科研基金 (96JDQN)~~
