title: Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune disease that affects people of all ages and ethnicities.
  
  
  OBJECTIVE
  To explore the relationship between age at disease onset and many of the diverse manifestations of SLE. Additionally, to determine the relationship between age of disease onset and genetic risk in patients with SLE.
  
  
  METHODS
  The relationship between the age at disease onset and SLE manifestations were explored in a multi-racial cohort of 1317 patients. Patients with SLE were genotyped across 19 confirmed genetic susceptibility loci for SLE. Logistic regression was used to determine the relationships between the number of risk alleles present and age of disease onset.
  
  
  RESULTS
  Childhood-onset SLE had higher odds of proteinuria, malar rash, anti-dsDNA antibody, haemolytic anaemia, arthritis and leucopenia (OR=3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively; p values <0.0001, 0.0004, 0.0005, 0.0024, 0.0114, 0.045, respectively). In female subjects, the odds of having cellular casts were 2.18 times higher in childhood-onset than in adult-onset SLE (p=0.0027). With age of onset ≥50, the odds of having proteinuria, cellular casts, anti-nRNP antibody, anti-Sm antibody, anti-dsDNA antibody and seizures were reduced. However, late adult-onset patients with SLE have higher odds of developing photosensitivity than early adult-onset patients. Each SLE-susceptibility risk allele carried within the genome of patients with SLE increased the odds of having a childhood-onset disease in a race-specific manner: by an average of 48% in Gullah and 25% in African-Americans, but this was not significant in Hispanic and European-American lupus patients.
  
  
  CONCLUSIONS
  The genetic contribution towards predicting early-onset disease in patients with SLE is quantified for the first time. A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration.
authors.affiliation: Arthritis & Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Webb
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.forename: Emily C
authors.initials: EC
authors.lastname: Somers
authors.forename: Travis
authors.initials: T
authors.lastname: Hughes
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: Elena
authors.initials: E
authors.lastname: Sanchez
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.forename: Gail
authors.initials: G
authors.lastname: Bruner
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Richardson
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009825:Oklahoma / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D055815:Young Adult