title: Analysis of maternal-offspring HLA compatibility, parent-of-origin effects, and noninherited maternal antigen effects for HLA-DRB1 in systemic lupus erythematosus.
abstract: OBJECTIVE
  Genetic susceptibility to systemic lupus erythematosus (SLE) is well established, with the HLA class II DRB1 and DQB1 loci demonstrating the strongest association. However, HLA may also influence SLE through novel biologic mechanisms in addition to genetic transmission of risk alleles. Evidence for increased maternal-offspring HLA class II compatibility in SLE and differences in maternal versus paternal transmission rates (parent-of-origin effects) and nontransmission rates (noninherited maternal antigen [NIMA] effects) in other autoimmune diseases have been reported. Thus, we investigated maternal-offspring HLA compatibility, parent-of-origin effects, and NIMA effects at DRB1 in SLE.
  
  
  METHODS
  The cohort comprised 707 SLE families and 188 independent healthy maternal-offspring pairs (total of 2,497 individuals). Family-based association tests were conducted to compare transmitted versus nontransmitted alleles (transmission disequilibrium test) and both maternally versus paternally transmitted (parent-of-origin) and nontransmitted alleles (using the chi-square test of heterogeneity). Analyses were stratified according to the sex of the offspring. Maternally affected offspring DRB1 compatibility in SLE families was compared with paternally affected offspring compatibility and with independent control maternal-offspring pairs (using Fisher's test) and was restricted to male and nulligravid female offspring with SLE.
  
  
  RESULTS
  As expected, DRB1 was associated with SLE (P < 1 x 10(-4)). However, mothers of children with SLE had similar transmission and nontransmission frequencies for DRB1 alleles when compared with fathers, including those for the known SLE risk alleles HLA-DRB1*0301, *1501, and *0801. No association between maternal-offspring compatibility and SLE was observed.
  
  
  CONCLUSIONS
  Maternal-offspring HLA compatibility, parent-of-origin effects, and NIMA effects at DRB1 are unlikely to play a role in SLE.
authors.affiliation: University of California, Berkeley, California 94720-7356, USA.
authors.forename: Paola G
authors.initials: PG
authors.lastname: Bronson
authors.forename: Leanne K
authors.initials: LK
authors.lastname: Komorowski
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Ramsay
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: May
authors.forename: Janelle
authors.initials: J
authors.lastname: Noble
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lane
authors.forename: Glenys
authors.initials: G
authors.lastname: Thomson
authors.forename: Frans H
authors.initials: FH
authors.lastname: Claas
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Moser
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: Timothy
authors.initials: T
authors.lastname: Behrens
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D011795:Surveys and Questionnaires
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen