title: Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus.
abstract: OBJECTIVE
  Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus.
  
  
  METHODS
  4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria.
  
  
  RESULTS
  Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10(-6), OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing.
  
  
  CONCLUSIONS
  Signifi cant associations were found between clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future.
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors: Elena
authors: E
authors: Sanchez
authors: Ajay
authors: A
authors: Nadig
authors: Bruce C
authors: BC
authors: Richardson
authors: Barry I
authors: BI
authors: Freedman
authors: Kenneth M
authors: KM
authors: Kaufman
authors: Jennifer A
authors: JA
authors: Kelly
authors: Timothy B
authors: TB
authors: Niewold
authors: Diane L
authors: DL
authors: Kamen
authors: Gary S
authors: GS
authors: Gilkeson
authors: Julie T
authors: JT
authors: Ziegler
authors: Carl D
authors: CD
authors: Langefeld
authors: Graciela S
authors: GS
authors: Alarcón
authors: Jeffrey C
authors: JC
authors: Edberg
authors: Rosalind
authors: R
authors: Ramsey-Goldman
authors: Michelle
authors: M
authors: Petri
authors: Elizabeth E
authors: EE
authors: Brown
authors: Robert P
authors: RP
authors: Kimberly
authors: John D
authors: JD
authors: Reveille
authors: Luis M
authors: LM
authors: Vilá
authors: Joan T
authors: JT
authors: Merrill
authors: Juan-Manuel
authors: JM
authors: Anaya
authors: Judith A
authors: JA
authors: James
authors: Bernardo A
authors: BA
authors: Pons-Estel
authors: Javier
authors: J
authors: Martin
authors: So-Yeon
authors: SY
authors: Park
authors: So-Young
authors: SY
authors: Bang
authors: Sang-Cheol
authors: SC
authors: Bae
authors: Kathy L
authors: KL
authors: Moser
authors: Timothy J
authors: TJ
authors: Vyse
authors: Lindsey A
authors: LA
authors: Criswell
authors: Patrick M
authors: PM
authors: Gaffney
authors: Betty P
authors: BP
authors: Tsao
authors: Chaim O
authors: CO
authors: Jacob
authors: John B
authors: JB
authors: Harley
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
authors: Amr H
authors: AH
authors: Sawalha
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008179:Lupus Erythematosus, Discoid / Q000208:ethnology / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D008181:Lupus Nephritis / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019226:Oral Ulcer / Q000208:ethnology / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult