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

Br J Dermatol. 2010 Nov;163(5):935-40. doi: 10.1111/j.1365-2133.2010.09928.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Histamine / genetics*
  • Receptors, Histamine H4
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • HRH4 protein, human
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4