1 research outputs found
Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases.
We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were
analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to
SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by
sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 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 C4 genetics strongly
contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid
variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals.MCIN/AEI by "ERDF A way of making Europe" RTI2018101332-B-100Red de Investigacion en Inflamacion y Enfermedades Reumaticas (RIER) from Instituto de Salud Carlos III RD16/0012/0013Innovative Medicines Initiative 1 & 2 Joint Undertaking (JU) 115565
831434European Union's FP7 and Horizon 2020 research and innovation programsEFPIAJuan de la Cierva Incorporacion program - MCIN/AEI IJC2018-035131-