甘露聚糖结合凝集素突变型等位基因与SLE关联的研究

收集系统性红斑狼疮(SLE)患者和普通人群血标本,提取白细胞基因组DNA,以多聚酶链反应扩增目的基因片段,应用荧光探针杂交技术检测甘露聚糖结合凝集素(MBL)基因GGC54GAC、GGA57GAA和CGT52TGT点突变(分别称为等位基因B、C、D,所有突变型统称为O,野生型即A),分析MBL突变型等位基因与SLE及其严重程度的关系。74例SLE患者中,检出等位基因型A/B24例(32.4%)、B/B5例(6.8%)、A/C2例(2.7%)、A/D1例(1.4%)和B/C2例(2.7%),B、C、D的频率为0.250、0.028和0.007,突变型等位基因O的频率为0.285;95例对照组中,检出A/B22例(23.2%)、B/B2例(2.1%)和A/C1例(1.1%),B、C的频率分别为0.137和0.005,O的频率为0.142;两者比较,其突变等位基因的分布有显著差异(P<0.05)。等位基因型O/O纯合子SLE患者肾脏损害的发生率达100%,而A/A或A/O型病人分别为35.0%和37.0%,存在非常显著差异(P<0.01)。因此,MBL突变型等位基因是SLE的易感因素并与肾脏累及有关。

Association between mutant alleles of mannan-binding lectin gene and systemic lupus erythematosus

Blood samples of patients with systemic lupus erythematosus (SLE) and healthy individuals from population of Guangdong Province were collected for study. The genomic DNA from these samples was extracted from leukocytes, the target sequence amplified by PCR, and the mannan-binging lectin (MBL) gene was assayed by fluorescenct probe hybridization technique with visual monitoring. Three point mutations, GGC54GAC, GGA57GAA and GGT52TGT, named as allele B, C and D respectively (all the mutants named as O, while the wild type as A)were found, The association between the mutant alleles of MBL gene and SLE and its severity was analyzed. It was found among 74 patients with SLE, 24 cases(32.4%) belonged to the genotype A/B, 5 cases (6.8%) to genotype B/B, 2 cases (2.7%) to genotype A/C, one case(1.1%) to genotype A/D and 2 cases (2.7%) to B/C. The frequencies of alleles B, C, D and O were 0.250, 0.028, 0.007 and 0.285 respectively. In 95 cases of healthy controls, 22 cases (23.2%) belonged to genotype A/B, 2 cases (2.1%) to genotype B/B, and one case (1.1%) to genotype A/C and the frequencies of alleles B, C and O were 0.137, 0.005 and 0.142 respectively. It was evident from the above analysis, there existed significant differences among these two groups. In patients who had renal damages, there was a significant over-representation of allele O/O (100%) in comparison with those of allele A/A and A/O (35.0% and 37.0%). From the above analysis, it is clear that MBL mutant alleles may be considered as a risk factor for SLE and they are associated with severity of disease.