Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis.
BACKGROUND
Atopic dermatitis (AD) is a chronic skin disease affecting more than 15% of children and 2% of adults. A strong connection between genetic factors and AD has been described for a long time. Histamine receptor H4 (HRH4) has been shown to be related to different kinds of allergic and autoimmune disorders. However, an association between HRH4 and AD has not yet been reported.


OBJECTIVE
To examine a possible association between HRH4 and AD.


METHODS
Genomic DNA from 301 patients with AD and 313 healthy controls was extracted and three exons of HRH4 were sequenced.


RESULTS
We found three new single nucleotide polymorphisms (SNPs) in HRH4 which were significantly associated with AD: ss142022671 [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.24-2.81; P = 0.002], ss142022677 (OR 4.40, 95% CI 2.42-8.00; P = 1.5 x 10(-7)) and ss142022679 (OR 4.26, 95% CI 2.38-7.61; P = 1.3 x 10(-7)). The SNPs ss142022677 and ss142022679 were found to be in strong linkage disequilibrium (D' = 0.98; r(2) = 0.92). Two-SNP haplotype analysis (ss142022677 and ss142022679) showed that the major AA haplotype was protective against AD (OR 0.22, 95% CI 0.12-0.40; P = 3.1 x 10(-8)) and the minor TT haplotype was significantly associated with AD (OR 4.13, 95% CI 2.27-7.54; P = 6.6 x 10(-7)). In addition, in a three-SNP haplotype analysis (ss142022671, ss142022677 and ss142022679), the major TAA haplotype was protective against AD (OR 0.46, 95% CI 0.31-0.69; P = 0.0001), while the complementary ATT haplotype was found to be significantly associated with AD (OR 3.81, 95% CI 2.03-7.14; P = 8.3 x 10(-6)).


CONCLUSIONS
Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD.
Yu
B
B
Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong 518036, China.
Shao
Y
Y
Zhang
J
J
Dong
X L
XL
Liu
W L
WL
Yang
H
H
Liu
L
L
Li
M H
MH
Yue
C F
CF
Fang
Z Y
ZY
Zhang
C
C
Hu
X P
XP
Chen
B C
BC
Wu
Q
Q
Chen
Y W
YW
Zhang
W
W
Wan
J
J
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics*; D000074040:Receptors, Histamine H4; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4