背景:骨关节炎( osteoarthritis,OA)是最常见的关节炎,尤其在老年人群中发病率更高,它是包括遗传因素在内的多因素致病疾病.已有多项研究发现,许多基因与OA的易感性有密切关系.胰岛素样生长因子1(insulin likegrowth factor 1,IGF-1)可以促进软骨细胞合成软骨中的细胞外基质.IGF-1及其受体在软骨的发育及成年后重塑阶段均具有重要功能,并可能与OA的病因具有相关性.目的:IGF-1基因启动子区域- 1245C/T位点(rs5767)单核苷酸多态性(single nucleotide polymorphisms,SNP)与膝关节OA的关系.方法:采用序列特异性引物PCR及探针法,检测中国汉族人群中具有临床症状且有影像学证据的524例原发性膝关节OA患者与540例健康对照者IGF-1基因启动子区域- 1245C/T位点等位基因分布,分析- 1245C/T位点等位基因与膝关节OA的相关性.结果:OA组与正常对照组比较,IGF-1基因启动子区域- 1245C/T位点的基因型频率及等位基因频率分布无显著性差异(P =0.35、0.14).按OA严重程度分组(中重度组患者均为K/L分级3、4级,轻度组为K/L分级2级),中重度组与正常对照组比较,基因型分布无显著性差异(P=0.10),等位基因频率分布有显著性差异(P=0.04)；但CC型与其它基因型(TT、TC)分布有显著性差异(P=0.03).正常对照组中TT+TC所占比例较中重度OA组多,OR=1.36,CI=[1.03,1.80].逻辑回归分析示,上述差异为年龄、BMI及性别差异所致,与rs35767的等位基因、基因型频率分布无显著相关性.结论:中国汉族人群的OA易感性与年龄、BMI、性别构成相关,与IGF-1基因启动子区域- 1245C/T位点( rs35767)基因多态性可能无关.%Background: Osteoarthritis (OA) , is the most common arthritis, especially in the elderly. Epidemiological studies haveshown that OA has a strong genetic component and several susceptibility genes for OA have been identified. Insulin - like growth factor 1 (IGF - 1 ) stimulates the synthesis of extracellular matrix ( ECM ) in cartilage. IGF - 1 and its receptor play an important role in cartilage formation both during developmental stages and remodeling of adult cartilage, and may be relevant to the etiology of OA.Objective; To evaluate the relationship between the single nucleotide polymorphisms (SNPs) of insulin-like growth factor 1 (IGF-1) rs35767 and knee osteoarthritis (OA).Methods: The IGF-1 SNP was genotyped in 524 patients with knee OA and 540 healthy control subjects and their association was evaluated statistically.Results: There were no significant differences of genotypic frequency and allele frequency between OA patients and health controls (P = 0. 35, 0. 14). A positive association was found for patients with severe/moderate knee OA versus controls in the comparisons of CC with other genotypes ( OR = 1. 36, CI = [ 1. 03 , 1. 80 ] , P = 0. 03) and allelic frequency ( OR = 1.25,CI= [1.02,1. 54],P=0. 04). Logistic regression analysis showed that the differences were caused by age, BMI and sex, and there was no significant difference between the polymorphism of IGF-1 rs35767 and knee OA susceptibility.Conclusions; The knee OA susceptivity is correlated to age, BMI and gender, but not correlated to the polymorphism of IGF-1 rs35767 in Han people of China.
展开▼
