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.


OBJECTIVE
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).


CONCLUSIONS
CNVs of the HRH4 gene are associated with SLE.
Yu
B
B
Department of Dermatology, Shenzhen Hospital Peking University, Shenzhen, Guangdong, China.
Shao
Y
Y
Li
P
P
Zhang
J
J
Zhong
Q
Q
Yang
H
H
Hu
X
X
Chen
B
B
Peng
X
X
Wu
Q
Q
Chen
Y
Y
Guan
M
M
Wan
J
J
Zhang
W
W
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics*; D000074040:Receptors, Histamine H4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
C418607:HRH4 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4