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.
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.
Authors: Roxana del Rio; Rajkumar Noubade; Naresha Saligrama; Emma H Wall; Dimitry N Krementsov; Matthew E Poynter; James F Zachary; Robin L Thurmond; Cory Teuscher Journal: J Immunol Date: 2011-12-05 Impact factor: 5.422
Authors: Pertti Panula; Paul L Chazot; Marlon Cowart; Ralf Gutzmer; Rob Leurs; Wai L S Liu; Holger Stark; Robin L Thurmond; Helmut L Haas Journal: Pharmacol Rev Date: 2015-07 Impact factor: 25.468