An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans |
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| Authors: | James M. Kelley, Laura B. Hughes, Jeffrey D. Faggard, Maria I. Danila, Monica H. Crawford, Yuanqing Edberg, Miguel A. Padilla, Hemant K. Tiwari, Andrew O. Westfall, Graciela S. Alarc n, Doyt L. Conn, Beth L. Jonas, Leigh F. Callahan, Edwin A. Smith, Richard D. Brasington, Jr, David B. Allison, Robert P. Kimberly, Larry W. Moreland, Jeffrey C. Edberg, S. Louis Bridges, Jr |
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| Affiliation: | James M. Kelley, Laura B. Hughes, Jeffrey D. Faggard, Maria I. Danila, Monica H. Crawford, Yuanqing Edberg, Miguel A. Padilla, Hemant K. Tiwari, Andrew O. Westfall, Graciela S. Alarcón, Doyt L. Conn, Beth L. Jonas, Leigh F. Callahan, Edwin A. Smith, Richard D. Brasington, Jr, David B. Allison, Robert P. Kimberly, Larry W. Moreland, Jeffrey C. Edberg, and S. Louis Bridges, Jr |
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| Abstract: | Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ~1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10−26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p | |
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