title: Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry.
abstract: 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.
  
  
  CONCLUSIONS
  These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.
authors: Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. ramosp@musc.edu
authors: Paula S
authors: PS
authors: Ramos
authors: James C
authors: JC
authors: Oates
authors: Diane L
authors: DL
authors: Kamen
authors: Adrienne H
authors: AH
authors: Williams
authors: Patrick M
authors: PM
authors: Gaffney
authors: Jennifer A
authors: JA
authors: Kelly
authors: Kenneth M
authors: KM
authors: Kaufman
authors: Robert P
authors: RP
authors: Kimberly
authors: Timothy B
authors: TB
authors: Niewold
authors: Chaim O
authors: CO
authors: Jacob
authors: Betty P
authors: BP
authors: Tsao
authors: Graciela S
authors: GS
authors: Alarcón
authors: Elizabeth E
authors: EE
authors: Brown
authors: Jeffrey C
authors: JC
authors: Edberg
authors: Michelle A
authors: MA
authors: Petri
authors: Rosalind
authors: R
authors: Ramsey-Goldman
authors: John D
authors: JD
authors: Reveille
authors: Luis M
authors: LM
authors: Vilá
authors: Judith A
authors: JA
authors: James
authors: Joel M
authors: JM
authors: Guthridge
authors: Joan T
authors: JT
authors: Merrill
authors: Susan A
authors: SA
authors: Boackle
authors: Barry I
authors: BI
authors: Freedman
authors: R Hal
authors: RH
authors: Scofield
authors: Anne M
authors: AM
authors: Stevens
authors: Timothy J
authors: TJ
authors: Vyse
authors: Lindsey A
authors: LA
authors: Criswell
authors: Kathy L
authors: KL
authors: Moser
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
authors: Carl D
authors: CD
authors: Langefeld
authors: John B
authors: JB
authors: Harley
authors: Gary S
authors: GS
authors: Gilkeson
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics*; D042967:Electron Transport Complex I; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005980:Glutathione Reductase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D001741:Black or African American
chemical_list: C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D009245:NADH Dehydrogenase; D005980:Glutathione Reductase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human
keywords: AFRICAN AMERICANS; GENETIC ASSOCIATION STUDIES; OXYGEN COMPOUNDS; SINGLE-NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS
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