系统性红斑狼疮患者16q12精细定位研究

目的预初研究提示16q12区与系统性红斑狼疮(SLE)存在关联,本研究旨在对该区域精细定位,以明确16号染色体与中国人SLE相关性。方法在16号染色体57.79~69.05cM(47218~52919kb)范围内选择8对微卫星标记(D16S540、D16S3044、D16S409、D16S517、D16S3136、D16S416、D16S419和D16S3034),扩增288个SLE患者家系DNA,产物经377DNA测序仪电泳,所得数据由Genescan软件收集进行基因分型,以ETDT及Genehunter进行连锁不平衡分析。结果D16S409及D16S517与SLE存在传递不平衡(P=0.0048和P<0.00001)。D16S517中,271bp等位基因优先传递给患病子代(P<0.00001),277bp等位基因则优先传递给正常子代(P<0.001)。结论研究结果证实人类SLE在16号染色体上存在疾病易感基因,中国人群16q12区(58.46cM,49Mb附近)与SLE发病相关联。

Fine mapping of 16q12 in systemic lupus erythematosus patients

Objective To fine map the susceptability loci in chromosome 16 in Chinese SLE cohort since preliminary study has shown that 16q12 might be associated with systemic lupus erythematosus (SLE). Methods Eight microsatellite markers in chromosome 16 (D16S540, D16S3044, D16S409, D16S517, D16S3136, D16S416, D16S419 and D16S3034) spanning from 57.79 cM to 69.05 cM (47 218 kb to 52 919 kb) were genotyped in 288 SLE families by fluorescence based genotyping technology.Evidence for linkage disequilibrium was assessed using the extended transmission disequilibrium test (ETDT) program and Genehunter software. Results With the ETDT, evidence for linkage disequilibrium of the marker D16S409 (P=0.0048) and D16S517 (P<0.000 01) in SLE was found. It was observed that 271 bp allele of D16S517 showed a marked preferential transmission tendency (P<0.000 01), while 277 bp allele was found to be transmitted less frequent than expected (P<0.001). Genehunter analysis was concordant to ETDT. Conclusion The results confirm that there are susceptability loci in chromosome 16 and 16q12 (in 58.46 cM and around 49 Mb) for SLE.