Association between Common Variants in VEGFA Gene and the Susceptibility of Primary Knee Osteoarthritis

OBJECTIVES: This study aimed to analyze the relationship between vascular endothelial growth factor A (VEGFA) gene polymorphisms, plasma VEGFA, and the susceptibility of knee osteoarthritis (OA). DESIGN: A total of 404 subjects, 202 knee OA subjects and 202 healthy volunteers, were enrolled into the study. Four distinct polymorphisms of the VEGFA gene were evaluated using polymerase chain reaction-restriction fragment length polymorphism: −2578C/A (rs699947), −1154G/A (rs1570360), −634C/G (rs2010963), and +936C/T (rs3025039). Plasma VEGFA levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: The most common nucleotides in both knee OA subjects and healthy controls were CC for −2578C/A, GG for −1154G/A, CG for −634C/G, and CC for +936C/T in the VEGFA gene. Genotype distribution and allele frequencies of VEGFA −2578C/A, −1154G/A, −634C/G, and +936C/T single nucleotide polymorphisms did not differ between OA patients and the controls. Plasma VEGFA levels showed no difference between OA patients and the controls. In contrast, plasma VEGFA levels of −634C/C genotype were significantly higher in OA patients than in the controls (P = 0.035). According to the −2578A/A genotype, patients with early stage OA had a higher odds ratio than those with advanced stage OA (P = 0.023). CONCLUSIONS: VEGFA −2578C/A (rs699947), −1154G/A (rs1570360), −634C/G (rs2010963), and +936C/T (rs3025039) polymorphisms may not be responsible for OA susceptibility in the Thai population. However, the OA patients with A/A genotype at the −2578C/A seemed to have a lower potential risk of developing severe OA than those with the C/A and C/C genotypes. These findings would help elucidate and facilitate a better understanding of the genetic fundamentals of OA.