Research concerning the genes responsible for osteoarthritis by association study and sib-pair linkage analysis

为了寻找骨关节炎的致病基因，对模型鼠与骨性关节炎的致病基因进行了关联研究，并进行了同胞对连锁分析。1.收集骨性关节炎患者的基因组DNA，收集173例散发性骨性关节炎患者和29例家系患者(38对同胞)的基因组DNA，2.骨关节炎模型鼠的致病基因分析。对AnkH基因全长c DNA和启动子区域的核苷酸序列进行了分析。以40份基因组DNA为材料，采用聚合酶链式反应-单链构象多态性分析和直接测序法对Ankh基因的序列变异进行了研究。共发现5个多态：编码区A1303G，非翻译区G1831A，5‘非翻译区8个碱基对缺失，启动子区域-785A/G和-639DelC。对0A患者202例和非OA对照103例进行单因素方差检验，分析其与骨性关节炎的相关性。发现51非翻译区8个碱基对缺失与骨质疏松症之间存在关联。所以它被找到了。提示AnkH基因在骨性关节炎的病因学中有一定的影响。3.成立。SIB-配对连锁分析收集的家庭病例样本不足以进行同胞配对连锁分析。进一步收集是有必要的。

In order to search die genes responsible for osteoarthritis (OA), association study between the gene responsible for the model mouse and osteoarthritis were performed and sib-pair linkage analysis were projected,1. Collecting genomic DNA of osteoarthritis patientsGenomic DNAs of 173 sporadic cases and 29 family cases (38 sibpairs), who have osteoarthritis without influence of injury, were collected,2. Analysis of the gene responsible for the osteoarthritis model mouseAssociation, study between the gene responsible for the model mouse and osteoarthritis was performed, A human homologue of mouse ank, which is responsible, for the OA model mouse, was cloned. The nucleotide sequence of full-length cDNA and promoter region of the ANKH gene was elucidated. Using 40 samples of genomic DNA, sequence variances in the ANKH gene were searched by PCR-SSCP and direct sequencing method. Five polymorphisms were found, A1303G in coding region, G1831A in 31untranslated region, eight-base-pairs deletionin 5' untranslated region, -785A/G and -639 delC in the promoter region. Using 202 samples of 0 A patients and 103 samples of non-OA controls, association between these polymorphisms and OA were analyzed by qui-square test. An association between eight-base-pairs deletion in 51untranslated region and OA was So it found. So it was found. Suggested that the ANKH gene has influence in the etiology of osteoarthritis. Found.3. Sib-pair linkage analysisCollected samples of family cases are not enough to perform the sib -pair linkage analysis. Further collection is necessary.