title: TNFAIP3 and IL12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort.
abstract: BACKGROUND
  Psoriasis vulgaris is a common chronic inflammatory skin disease. Development of early onset psoriasis is, to some extent, genetically determined and a strong association with the major histocompatibility complex HLA-Cw6 has been demonstrated. The use of genome-wide association studies has highlighted novel genes associated with the development of psoriasis as IL12B, IL23R, TNFAIP3 and IL13 for instance. The majority of these studies were performed on cohorts of European descent.
  
  
  OBJECTIVE
  To determine whether inter-ethnic differences exist in the genetic susceptibility to psoriasis, we genotyped single-nucleotide polymorphism variations in the vicinity of candidate genes in 132 Egyptian patients and 175 healthy controls.
  
  
  METHODS
  Blood samples of patients and controls were screened for nucleotide polymorphisms in four candidate genes by TaqMan single-nucleotide polymorphisms Genotyping Assays.
  
  
  RESULTS
  We found a significant association between psoriasis and the single-nucleotide polymorphism rs610604, within the TNFAIP3 gene. The TNFAIP3 gene is involved in the TNF-α signalling cascade (P-value: 0.004952), a key step in the pathogenesis of psoriasis. Although there was no significant association found between rs610604 (IL12B) and rs11209026 (IL23R) in this population, the interaction of these two genes showed a significant association with psoriasis (P-value: 0.025). Moreover, when selecting the patients with early disease onset (less than 30 years), we also found that the association of IL12B and psoriasis was highly significant (P-value 1.14 × 10(-12)). No association between rs20541 (IL13) and psoriasis was observed in our Egyptian cohort.
  
  
  CONCLUSIONS
  Replicating the association of single-nucleotide polymorphisms in the TNFAIP3, IL12B and IL23R genes with psoriasis vulgaris, in subjects from different ethnic backgrounds, underlines their importance in the pathogenesis of the disease. In contrast, the lack of any association between rs20541 (IL13) and psoriasis in our Egyptian cohort suggests the existence of important inter-ethnic genetic differences in psoriasis susceptibility.
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Haase
authors.affiliation: Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.
authors.forename: H
authors.initials: H
authors.lastname: Mosaad
authors.affiliation: Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: M A
authors.initials: MA
authors.lastname: Eldarouti
authors.affiliation: Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: A Z
authors.initials: AZ
authors.lastname: Elramly
authors.affiliation: Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: N
authors.initials: N
authors.lastname: Samir
authors.affiliation: Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: M M
authors.initials: MM
authors.lastname: Abdelhady
authors.affiliation: Department of Dermatology, Zagazig University, Zagazig, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Samir
authors.affiliation: Department of Dermatology, Zagazig University, Zagazig, Egypt.
authors.forename: I
authors.initials: I
authors.lastname: El-Gharib
authors.affiliation: Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.
authors.forename: S
authors.initials: S
authors.lastname: Salah
authors.affiliation: Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.
authors.forename: F A
authors.initials: FA
authors.lastname: El-Shennawy
authors.affiliation: Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.
authors.forename: Y
authors.initials: Y
authors.lastname: Mosaad
authors.affiliation: Department of Dermatology, Tanta University, Tanta, Egypt.
authors.forename: N
authors.initials: N
authors.lastname: Elwan
authors.affiliation: Department of Dermatology, Mansoura University, Mansoura, Egypt.
authors.forename: H
authors.initials: H
authors.lastname: Salem
authors.affiliation: Department of Dermatology, Mansoura University, Mansoura, Egypt.
authors.forename: S
authors.initials: S
authors.lastname: Abdelgaber
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Recke
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Möller
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ibrahim
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004534:Egypt / Q000453:epidemiology; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha
chemical_list: D004268:DNA-Binding Proteins; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3