Method: FcgRIIC SNP 202T>C and the intron 6 SNPs (SNP6L-A>G and SNP6R-C>G) were genotyped in 833 African American (AA) healthy controls and 764 AA RA patients using Pyrosequecing methodology. SNP allele, genotype, and haplotype distributions were compared between RA and healthy controls. The functions of the FcgRIIC SNP were investigated in mini-gene and transfected cell systems.
Result: Our genotyping data demonstrated that the SNP 202C (open-reading frame allele) is significantly associated with RA susceptibility (P = 0.0002, Odds Ratio 1.584; 95% CI: 1.238–2.027) in AA. In addition, the frequency of the SNP-6L G allele (which forms a canonical splicing donor motif) is significantly increased in AA RA patients compared to controls (P = 0.0007, OR = 1.923, 95% CI 1.312-2.819). No association of SNP-6R alleles with RA susceptibility was observed in AA (P = 0.9400, OR = 1.005, CI = 0.874–1.156). The haplotype 202C/6L-G/6R-G is a major risk factor for RA in African Americans (P = 0.015, OR 3.533; 95% CI: 1.278-9.772). Functionally, the expression of SNP 202T allele enhanced the inhibitory FcgRIIB expression in human B cells. Furthermore, the intron 6 SNPs are the main origin of the various FcgRIIC mRNA species and the 202C/6L-G/6R-G is the sole FcgRIIC SNP haplotype capable of producing an activating receptor.
Conclusion: The functional FcgRIIC SNP haplotype 202C/6L-G/6R-G is a genetic marker for RA in AA and may have important biological consequences.
Disclosure: J. Wu, None; X. Li, None; R. Lin, None; H. Wiener, None; H. Tiwari, None; C. Liu, None; T. Ptacek, None; J. C. Edberg, None; S. L. Bridges Jr., None; R. P. Kimberly, None.