Exome-Wide Association Analysis Suggests LRP2BP as a Susceptibility Gene for Endothelial Injury in Systemic Sclerosis in the Han Chinese Population.

摘要: Genetic factors play a key role in the pathogenesis of autoimmune diseases, whereas disease-causing variants remain largely unknown. Herein, we performed an exome-wide association study systemic sclerosis Han Chinese population. In discovery stage, 527 patients with and 5,024 controls were recruited genotyped. validation study, independent sample set 479 1,096 examined. total, found that four signals reached genome-wide significance. Among them, rs7574865 (Pcombined = 3.87 × 10−12) located within signal transducer activator transcription 4 gene was identified previously using samples European ancestry. Additionally, another including three SNPs linkage disequilibrium might be unreported susceptibility loci epidermis differentiation complex region. Furthermore, two exon 3 IGHM (rs45471499, Pcombined = 1.15 × 10−9) upstream LRP2BP (rs4317244, 4.17 × 10−8) found. Moreover, rs4317244 as expression quantitative trait locus for regulates tight junctions, cell cycle, apoptosis endothelial lines. Collectively, our results revealed associated suggested importance pathogenesis. Given limited size discrepancies between previous further studies multiethnic populations are required verification.