• Medientyp: E-Artikel
  • Titel: Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
  • Beteiligte: Kerick, Martin; Acosta-Herrera, Marialbert; Simeón-Aznar, Carmen Pilar; Callejas, José Luis; Assassi, Shervin; Carreira, P.; Castellvi, I.; Ríos, R.; Portales, R. García; Fernández-Nebro, A.; García-Hernández, F. J.; Aguirre, M. A.; Fernández-Gutiérrez, B.; Rodríguez-Rodríguez, L.; de la Peña, P. García; Vicente, E.; Andreu, J. L.; de Castro, M. Fernández; López-Longo, F. J.; Fonollosa, V.; Guillén, A.; Espinosa, G.; Tolosa, C.; Pros, A.; [...]
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: npj Genomic Medicine
  • Sprache: Englisch
  • DOI: 10.1038/s41525-022-00327-8
  • ISSN: 2056-7944
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Copy number (CN) polymorphisms of complement<jats:italic>C4</jats:italic>play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of<jats:italic>C4</jats:italic>CN with systemic sclerosis (SSc) risk. Imputed total<jats:italic>C4, C4A</jats:italic>,<jats:italic>C4B</jats:italic>, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher<jats:italic>C4</jats:italic>CN confers protection to SSc, and deviations from CN parity of<jats:italic>C4A</jats:italic>and<jats:italic>C4B</jats:italic>augmented risk. The protection contributed per copy of<jats:italic>C4A</jats:italic>and<jats:italic>C4B</jats:italic>differed by sex. Stronger protection was afforded by<jats:italic>C4A</jats:italic>in men and by<jats:italic>C4B</jats:italic>in women.<jats:italic>C4</jats:italic>CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that<jats:italic>C4</jats:italic>genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of<jats:italic>HLA-DRB1</jats:italic>and<jats:italic>HLA-DPB1</jats:italic>as<jats:italic>C4</jats:italic>-independent signals.</jats:p>
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