Copy number variations of the human histamine H4 receptor gene are associated with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a complex genetic disease; the histamine H4 receptor (HRH4) has been shown to be related to different kinds of autoimmune disorders; and copy number variations (CNVs) have been found to be associated with various types of diseases. Objectives To explore a possible association between HRH4 (formerly H4R) CNVs and the risk of SLE. Methods Genomic DNA and RNA from 340 patients with SLE and 392 healthy controls were extracted, and CNVs and mRNA levels of HRH4 were examined. Results The expression of HRH4 mRNA was significantly increased in patients with SLE compared with controls. Amplification of HRH4 copy numbers significantly increased the risk of SLE [P < 0·001, odds ratio (OR) 2·26, 95% confidence interval (CI) 1·50–3·40]. HRH4 amplifications also positively correlated with the incidence of arthritis (P = 0·019, OR 1·96, 95% CI 1·11–3·47), and proteinuria (P < 0·001, OR 2·95, 95% CI 1·73–5·00) and antinuclear antibody abnormalities (P < 0·001, OR 2·97, 95% CI 1·66–5·33). Deletions of HRH4 copy numbers were protective against proteinuria (P = 0·03, OR 0·50, 95% CI 0·26–0·94). Conclusion CNVs of the HRH4 gene are associated with SLE.