title: Genetic variations within the promotor region of the human histamine H4 receptor gene in psoriasis patients.
abstract: Environmental triggers and genetic factors are supposed to lead to complex gene expression changes in psoriasis and interact in the manifestation of the disease. The histamine H4 receptor (HRH4) is functionally expressed on Th17 cells and plasmacytoid dendritic cells (pDCs) which play a prominent role in the pathogenesis of psoriasis. On pDCs a higher basal expression level of the HRH4 in psoriasis patients compared to healthy controls has been detected. The functional relationship between predisposing genetic variations in the HRH4 gene and psoriasis is yet not known. The aim of the study was to evaluate a possible association between single nucleotide polymorphisms (SNPs) in the HRH4 gene primarily in the promotor region and incidence, severity as well as special clinical features (nail involvement, arthritis, palmoplantar location) of psoriasis. For this approach genomic DNA from 206 patients with psoriasis and 213 healthy controls of Caucasian origin was extracted and three SNPs in the promotor region and one SNP located in an intron of the HRH4 gene were analysed by PCR and pyrophosphate DNA-sequencing. The genotype distributions and allele frequencies between the different groups were compared by chi-square test. The analysis of association between HRH4 polymorphisms and psoriasis was assessed by odds ratio with 95% confidence interval. The genotype distributions and allele frequencies of the four SNPs in the HRH4 gene did not show obvious differences between the whole group of psoriasis patients and healthy controls. However, there were differences by trend in subgroup analysis: The mutant genotypes (A/G) of rs17203314 and (G/A) of rs615283 were more frequent in patients with severe psoriasis PASI≥30 (34.8% and 34.8%) when compared to the control groups (23.5% and 27.2%), respectively. The mutant G/A genotype of rs615283 was significantly more frequent in patients with moderate-to-severe psoriasis PASI≥10 when compared to mild psoriasis PASI<10 (33.3% vs 21.7%, p=0.022). For rs524149 and rs17797945 the wildtype CC genotype was more frequent by trend in moderately-to-severely affected patients with PASI≥10 (85.2% and 63.0%) when compared to the group with mild psoriasis PASI<10 (77.0% and 49.4%), respectively. Furthermore, a significant association of rs615283 with psoriasis palmoplantaris was detected. In conclusion our study suggests that genetic variations within the HRH4 gene might be associated with special clinical features of psoriasis. Further studies are needed in larger study populations to confirm the reported associations and investigate the functional relevance of the identified SNPs.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. Electronic address: Mommert.Susanne@mh-hannover.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mommert
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Lisanne
authors.initials: L
authors.lastname: Ratz
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Kira
authors.initials: K
authors.lastname: Herwig
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Rost
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology; D000074040:Receptors, Histamine H4 / Q000235:genetics*
chemical_list: C418607:HRH4 protein, human; D000074040:Receptors, Histamine H4
keywords: Histamine H4 receptor (HRH4) gene; Psoriasis; Psoriasis area and severity index (PASI); Pyrophosphate DNA-sequencing; SNPs single nucleotide polymorphisms