为探讨宁夏回族原发性膝骨性关节炎(Osteoarthritis, OA)与瘦素受体基因(Leptin receptor, LEPR)A668G位点单核苷酸多态性(SNPs)之间的关系, 文章运用病例-对照研究, 通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术, 对148例兼具原发症状和影象证据的宁夏回族膝OA患者以及155名年龄、性别相匹配的对照群体进行LEPR A668G SNPs检测, 并进行测序验证, 分析LEPR基因多态性与膝OA的易感关联。研究表明, 膝OA组瘦素(Leptin, LEP)水平显著高于对照组(P<0.001), 血浆可溶性瘦素受体(sLEPR)水平较对照组明显降低(P<0.001), 膝OA组LEPR A668G位点AG/GA+GG基因型和G等位基因的分布频率和对照组存在差异(P=0.008和P=0.024)。研究结果提示, LEPR A668G位点的多态性可能与宁夏回族人群中膝OA易感性相关, 可以作为预测宁夏回族膝OA发病危险的遗传标记及早期防治的候选基因之一。
To investigate the association between primary knee osteoarthritis (OA) and single nucleotide polymorphism (SNP) (A668G) of leptin receptor gene (LEPR) in the Ningxia Hui population. A case-control association study has been adopted in this thesis. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis were performed to investigate the SNP of A668G site within LEPR from 148 patients with knee OA and 155 controls (asymptomatic and radiographically negative) with matched age and gender among Ningxia Hui population. In addition, genotypes of LEPR were verified by direct sequence analysis on PCR products. The result indicates that allele and genotype frequencies (P=0.024 and 0.008, respectively) in LEPR SNP A668G were significantly different in the knee OA patients group and control group, and in the knee OA patients group, the serum levels of leptin decreased significantly (P<0.001) and the serum levels of soluble leptin receptor increased significantly (P<0.001) compared with control group. Therefore, LEPR SNP A668G is associated with susceptibility to knee OA, which would be used as the genetic marker in predicting the risk of knee OA and would be one of the candidate genes in early prevention and con-trol.
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