TY - JOUR T1 - Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry JF - The Journal of Rheumatology JO - J Rheumatol SP - 842 LP - 849 DO - 10.3899/jrheum.120989 VL - 40 IS - 6 AU - Paula S. Ramos AU - James C. Oates AU - Diane L. Kamen AU - Adrienne H. Williams AU - Patrick M. Gaffney AU - Jennifer A. Kelly AU - Kenneth M. Kaufman AU - Robert P. Kimberly AU - Timothy B. Niewold AU - Chaim O. Jacob AU - Betty P. Tsao AU - Graciela S. Alarcón AU - Elizabeth E. Brown AU - Jeffrey C. Edberg AU - Michelle A. Petri AU - Rosalind Ramsey-Goldman AU - John D. Reveille AU - Luis M. Vilá AU - Judith A. James AU - Joel M. Guthridge AU - Joan T. Merrill AU - Susan A. Boackle AU - Barry I. Freedman AU - R. Hal Scofield AU - Anne M. Stevens AU - Timothy J. Vyse AU - Lindsey A. Criswell AU - Kathy L. Moser AU - Marta E. Alarcón-Riquelme AU - Carl D. Langefeld AU - John B. Harley AU - Gary S. Gilkeson Y1 - 2013/06/01 UR - http://www.jrheum.org/content/40/6/842.abstract N2 - Objective. Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. Methods. A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. Results. The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09–1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23–3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44–0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10–1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. Conclusion. These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups. ER -