Strong associations of psoriasis with antigen processing LMP and transport genes TAP differ by gender and phenotype.
Psoriasis, a skin disease with autoimmune features, can be triggered and exacerbated by genetic and environmental factors. Chemicals can break tolerance to self-antigens by interfering with antigen processing and presentation; therefore, proteins involved in antigen processing may affect susceptibility. We test here whether variants of immunoproteasome subunits LMP2 and LMP7, or antigen peptide transport proteins TAP1 (transporters associated with antigen presentation) and TAP2 are associated with psoriasis. We analyzed 7 single-nucleotide polymorphisms in 321 Caucasian (German) psoriasis patients and 235 unrelated controls by time-of-flight mass spectrometry, using the Sequenom platform. We found strong associations of psoriasis with variant alleles of LMP and TAP (OR(TAP_687): 3.3, 95% CI: 1.9-5.7). Genotype effects were generally stronger for males and LMP effects were mainly seen for psoriasis arthropathica. Our results will help define behavioral or drug treatment suggestions to patients and contribute to a better understanding of the role of low molecular weight chemicals in genetic susceptibility to autoimmune diseases.
Krämer
U
U
Institut für Umweltmedizinische Forschung, Forschung, Auf' m Hennekamp 50, Düsseldorf, Germany.
Illig
T
T
Grune
T
T
Krutmann
J
J
Esser
C
C
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology; D012727:Sex Characteristics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex