Association of genetic variations with knee osteoarthritis in Thais

Abstract

Osteoarthritis (OA), a common joint disorder in aging people, is characterized by the disintegration and loss of the articular cartilage. In addition to non-genetic factors such as age, sex, body weight and joint injury, OA also has a strong genetic background. This study is divided into two parts. The first part aims to evaluate the association between variations in ADAMTS14, ADAM12 and MMP1 genes and susceptibility to knee OA in Thai population. The study population consisted of 108 knee OA patients and 119 normal controls. The ADAMTS14 SNP (rs4747096; A/G) was genotyped by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP), while the ADAM12 SNP (rs3740199; C/G) and MMP1 SNP (rs1799750; 2G/1G) were genotyped by high resolution melt (HRM) analysis. The significant associations were achieved from the SNP in ADAMTS14 with female knee OA patients and ADAM12 with male knee OA patients. In contrast, no statistically significant association was found from the SNP in MMP1. The second part aims to identify genes with alternative splice variants in human synoviocytes. Among 32 candidate gene revealed from microarray data processing, HNRNPU and BRD4 were selected for further analysis by reverse transcriptase–polymerase chain reaction (RT-PCR) and real-time PCR. The results showed no alternative splicing in HNRNPU but revealed 2 isoforms of BRD4 that are BRD4[+7] and BRD4[-7]. The BRD4[-7] is the novel isoform which the expression was significantly decreased in knee OA patients, indicating its possible role in OA pathogenesis. In conclusion, the associations between SNPs in ADAMTS14 and knee OA in female, ADAM12 and knee OA in male, and the decreased level of BRD4[-7], a novel isoform of BRD4, and knee OA were found in this study.