Age at onset of rheumatoid arthritis: Association with polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and an intergenic locus between matrix metalloproteinase (MMP) 1 and 3 genes

Objective: The present paper aims to investigate whether polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and the loci of matrix metalloproteinase (MMP) 1 and 3 genes are associated with age at onset of RA. Methods: A sample of 413 hospital-based RA patients of Caucasian origin was studied. Common single-nucleotide polymorphisms (SNP) with likely importance were typed, including rs699947, rs833061, rs2010963 and rs3025039 in VEGFA, and rs1799750 in the MMP1 gene, rs3025058, rs679620 in the MMP3 gene and rs495366 located within the region between the MMP1 and MMP3 genes. Age at onset of RA was obtained on each patient. Demographic variables, smoking information, and a core set of clinical characteristics measured at recruitment were recorded. Hazard ratios (HR) that measured the effect size of genetic risk on age at RA onset were computed using Cox regression models. Results: The T allele at rs3025039 was associated with an increased risk of early onset (HR=1.25 [95% CI 1.0-1.58] for the risk over time; HR=1.84 [95% CI 1.20-2.83] for the risk of onset <40 years old). The AA genotype at rs495366 was also associated with an increased risk (HR=1.92 [95% CI 1.27-2.89] over time; HR=2.54 [95% CI 1.30-4.95] for onset <40 years old). These associations were independent of other risk factors such as sex, smoking and anti-CCP status. Conclusion: Polymorphisms in the VEGFA gene and the MMP1-3 intergenic locus may influence age at onset of RA.