摘要
目的通过检测系统性红斑狼疮(SLE)患者甘露糖结合凝集素(MBL)的血清水平及其基因变异情况,探讨MBL在SLE发病机制中的作用。方法以30名健康献血员为对照,以40例SLE患者为研究对象。通过固相ELISA方法检测MBL的血清水平。根据MBL2*LXPA(基因库X15422)单倍体序列设计了MBL外显子1区和启动子区的引物和荧光标记的寡核苷酸杂交探针,通过L ight Cyc ler实时PCR技术检测2组标本的基因变异情况。结果(1)SLE患者的MBL血清水平显著低于健康献血员(107.2μg/L对290.2μg/L,P<0.01)。(2)MBL基因外显子1区的突变以第54位密码子的突变为主,其突变率在SLE患者为37.1%(15/40),对照组为13.3%(5/30),两组比较χ2=3.914,P<0.05。(3)健康献血员和SLE患者在H/L位点均存在多态性,两组的L频率相当。(3)发生第54位密码子突变的SLE患者血清MBL水平显著下降,发生突变者与未发生突变者分别为141.7μg/L,49.8μg/L,两者比较P<0.01;两者的SLE活动指数(DAI)积分分别为12.87和7.44,P<0.01,且SLEDAI积分与MBL血清水平呈负相关(r=-0.48),启动子区H/L多态性与SLEDAI无关。结论发生MBL基因第54位密码子突变可能是SLE发病的易感因素;MBL的血清水平可能是SLE疾病活动性的潜在生物标记。
Objective To detect the serum level of mannose binding lectin （MBL） and its genovariation in systemic lupus erythematosus （SLE） patients and to investigate the role of MBL in the pathogenesis of SLE. Methods ELISA was used to measure the serum MBL level of 40 SLE patients and 30 healthy blood donors. Tm genotyping method was used for the first timer in China. Primers and specific fluorophore-labelled hybridization probes for the exon 1 and promoter regions of MBL gene were designed based on the haplotype MBL2^· LXPA（ GenBank X15422）. The genotyping of MBL in these two groups were performed using real-time PCR through Light Cycler Instrument. Results ① The serum MBL of the SLE patients was 107.2 μg/L, significantly lower than that of the healthy blood donors （ 290.2 μg/L, P = 0.0002）. ② MBL mutation in exon 1 region was mainly at codon 54, with a mutation rate of 37.1% in the SLE group, significantly higher than that of the control group （ 13.3 %, p = 0.049 ）. ③ Polymorphisms of H/L in MBL gene were present in both SLE patients and controls, and there was no difference in the L allele frequency between the two groups. ④ The serum MBL level of the SLE patients with MBL mutation in cedon 54 was 49.8 μg/L, significantly lower than that of the SLE patients without MBL mutation in cedon 54 （141.7 μg/L, P=0.000 27）. The SLE disease activity index （SLEDAI） of the SLE patients with MBL mutation in codon 54 was 7.44, significantly lower than that of the SLE patients without MBL mutation in codon 54 （12.87, P =0. 0029）. A negative correlation was observed between SLEDAI score and serum MBL （r = - 0. 48 ）. Conclusion Mutation occurring in MBL exon 1 region at cedon 54 may be a predisposing factor of the pathogenesis of SLE. Serum MBL may be a potential biomarker of disease activity in SLE patients.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2006年第7期463-467,共5页
National Medical Journal of China
