Sharma A C, Srivastava R N, Srivastava S R, Agrahari A, Singh A, Parmar D
Department of Orthopaedic Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India.
Developmental Toxicology Division, IITR, Lucknow, Uttar Pradesh, India.
J Postgrad Med. 2017 Jul-Sep;63(3):151-156. doi: 10.4103/jpgm.JPGM_450_16.
Osteoarthritis (OA) is a chronic degenerative disorder probably affected by both genetic and environmental causes. Bone morphogenetic proteins (BMPs) are bone-derived factors that can induce new bone formation. Single-nucleotide polymorphisms (SNPs) of BMP5 gene alters the transcriptional activity of the BMP5 promoter that has been involved in OA susceptibility. This case-control study investigated the association of rs1470527 and rs9382564 SNP of BMP5 gene with susceptibility to knee OA (KOA).
A total of 499 cases with radiographic KOA and 458 age- and sex-matched healthy controls were enrolled. Venous blood samples were obtained from all the cases as well as controls for polymerase chain reaction-restriction fragment length polymorphism.
The genotype distribution for rs1470527 and rs9382564 SNP was significantly different in cases and controls (P < 0.0001). Within both the SNPs of BMP5 gene, genotype CT and TT were significantly (P < 0.0001) associated with KOA as compared to the CC genotype. T allele of both the studied SNP was significantly associated with KOA (P < 0.0001). The allele frequencies of rs1470527 were 0.56(T) and 0.44(C) in cases and 0.33(T) and 0.67(C) in controls and in rs9382564 were 0.57(C) and 0.43(T) in cases and 0.71(C) and 0.29(T) in controls. Further in relation with clinical severity of OA, we observed signification association of TT genotype with both visual analog scale (P < 0.0001) and Western Ontario and McMaster Universities score (P < 0.05).
Our results indicate significant association of rs1470527 and rs9382564 polymorphism of BMP5 gene with KOA.
骨关节炎（OA）是一种慢性退行性疾病，可能受遗传和环境因素影响。骨形态发生蛋白（BMPs）是可诱导新骨形成的骨源性因子。BMP5基因的单核苷酸多态性（SNPs）改变了与OA易感性相关的BMP5启动子的转录活性。本病例对照研究调查了BMP5基因的rs1470527和rs9382564 SNP与膝骨关节炎（KOA）易感性的关联。
共纳入499例经影像学诊断的KOA患者和458例年龄及性别匹配的健康对照。采集所有病例和对照的静脉血样本，用于聚合酶链反应-限制性片段长度多态性分析。
rs1470527和rs9382564 SNP的基因型分布在病例组和对照组中存在显著差异（P < 0.0001）。在BMP5基因的两个SNP中，与CC基因型相比，CT和TT基因型与KOA显著相关（P < 0.0001）。两个研究SNP的T等位基因均与KOA显著相关（P < 0.0001）。rs1470527的等位基因频率在病例组中为0.56（T）和0.44（C），在对照组中为0.33（T）和0.67（C）；rs9382564的等位基因频率在病例组中为0.57（C）和0.43（T），在对照组中为0.71（C）和0.29（T）。进一步与OA的临床严重程度相关分析，我们观察到TT基因型与视觉模拟评分（P < 0.0001）和西安大略和麦克马斯特大学评分（P < 0.05）均存在显著关联。
我们的结果表明BMP5基因的rs1470527和rs9382564多态性与KOA显著相关。
