title: Polymorphisms of the ITGAM gene confer higher risk of discoid cutaneous than of systemic lupus erythematosus.
abstract: BACKGROUND
  Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear.
  
  
  RESULTS
  To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value  = 4.73×10(-11), OR  = 3.20, 95% CI  = 2.23-4.57). Significant association was also detected to SLE patients (P-value  = 8.29×10(-6), OR  = 2.14, 95% CI  = 1.52-3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value  = 3.59×10(-8), OR  = 3.76, 95% CI  = 2.29-6.18).
  
  
  CONCLUSIONS
  We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.
authors.affiliation: Department of Dermatology, Institute of Clinical Medicine and Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Järvinen
authors.forename: Anna
authors.initials: A
authors.lastname: Hellquist
authors.forename: Sari
authors.initials: S
authors.lastname: Koskenmies
authors.forename: Elisabet
authors.initials: E
authors.lastname: Einarsdottir
authors.forename: Jaana
authors.initials: J
authors.lastname: Panelius
authors.forename: Taina
authors.initials: T
authors.lastname: Hasan
authors.forename: Heikki
authors.initials: H
authors.lastname: Julkunen
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Marika
authors.initials: M
authors.lastname: Kvarnström
authors.forename: Marie
authors.initials: M
authors.lastname: Wahren-Herlenius
authors.forename: Filippa
authors.initials: F
authors.lastname: Nyberg
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Ulpu
authors.initials: U
authors.lastname: Saarialho-Kere
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D039481:CD11b Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005387:Finland; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008179:Lupus Erythematosus, Discoid / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D013548:Sweden
chemical_list: D039481:CD11b Antigen; D005819:Genetic Markers; C509295:ITGAM protein, human