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The integrin αvβ3, whose αv subunit is encoded by the  ITGAV  gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the  ITGAV  gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the  ITGAV  gene for association and linkage to RA in a family-based study from the European Caucasian population.  Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.  We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%;  P =  0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%;  P =  0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus50% of transmission;  P =  0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339;  P =  0.002, odds ratio = 1.94, 95% confidence interval = 1.3–2.9).  The rs3738919-C allele of the  ITGAV  gene is associated with RA in the European Caucasian population, suggesting  ITGAV  as a new minor RA susceptibility gene.

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study