Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis

Abstract

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. Objectives 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 × 10 -7) and ss142022679 (OR 4·26, 95% CI 2·38-7·61; P = 1·3 × 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 × 10 -8) and the minor TT haplotype was significantly associated with AD (OR 4·13, 95% CI 2·27-7·54; P = 6·6 × 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 × 10 -6). Conclusions Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD. © 2010 British Association of Dermatologists.