title: A-1012G promoter polymorphism of vitamin D receptor gene is associated with psoriasis risk and lower allele-specific expression.
abstract: Psoriasis is caused by a combination of genetic, immunologic, and environmental factors. The vitamin D receptor (VDR) is involved in antiproliferative and prodifferentiation pathways in keratinocytes and exerts immunosuppressive effects. We aimed to investigate possible associations between VDR polymorphisms and psoriasis susceptibility and to evaluate functional effects of potential psoriasis-associated polymorphisms. We genotyped 108 patients with psoriasis and 268 healthy controls at 5 VDR polymorphisms (A-1012G, FokI, BsmI, ApaI, and TaqI) by TaqMan allelic-discrimination real-time polymerase chain reaction. We found a significant increased overall risk of psoriasis for the VDR A-1012G promoter polymorphism (odds ratio [OR]=2.43, 95% confidence interval [CI]: 1.15-5.13; p=0.05). A significant higher frequency (p=0.035) of the A allele was found in psoriatic cases compared with controls. In a case-case analysis, a statistically significant association between A-1012G and family history emerged (p=0.033). Furthermore, a significant association of A-1012G risk genotypes with a lower expression of VDR mRNA emerged (p=0.0028). Our data show that VDR promoter A-1012G polymorphism is associated with psoriasis risk and suggest that this polymorphism may modulate psoriasis risk by affecting VDR expression.
authors: 1 Department of Internal Medicine and Medical Specialties, Unit of Dermatology, "Sapienza" University of Rome , Rome, Italy .
authors: Antonio Giovanni
authors: AG
authors: Richetta
authors: Valentina
authors: V
authors: Silvestri
authors: Simona
authors: S
authors: Giancristoforo
authors: Piera
authors: P
authors: Rizzolo
authors: Sara
authors: S
authors: D'Epiro
authors: Veronica
authors: V
authors: Graziano
authors: Carlo
authors: C
authors: Mattozzi
authors: Anna Sara
authors: AS
authors: Navazio
authors: Marco
authors: M
authors: Campoli
authors: Cristina
authors: C
authors: D'Amico
authors: Marco
authors: M
authors: Scarnò
authors: Stefano
authors: S
authors: Calvieri
authors: Laura
authors: L
authors: Ottini
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol