The association of variants in the ADRA1B gene with psoriasis could explain why variants in the IL-12B, ADRA1B and PTTG1 gene regions are associated with psoriasis.
To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B).
Case-control analysis revealed an association of IL12Brs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (OR = 0.66, 95%CI: 0.50-0.87, and OR = 0.41, 95%CI: 0.26-0.67, respectively), while HLA-C*06 allele carriers were more frequent in patients group (OR = 4.56, 95%CI: 3.41-6.10).
Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis.
Our data suggested the association of IL12B with the psoriasis, however no evidence was observed for the epistatic effect of IL12B with HLA-Cw6 among the psoriasis patients in India.
We observed that the patients carrying the risk genotypes of IL-12B (rs3212227) and IL-23R (rs2201841) conferred an increased susceptibility to psoriasis.
The results demonstrate allelic heterogeneity at IL12B and identify a high-risk MHC class I haplotype, consistent with the existence of multiple psoriasis effectors in the MHC.
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).
Strong additive effects when combining HLA-C*06 with IL23A, IL23R, IL12B, NFKB1 or TNIP1 were restricted to the severe cohort, indicating that activation of these pathways may influence disease severity in psoriasis.
We confirmed four known psoriasis susceptibility loci (IL12B, IFIH1, ERAP1 and RNF114; 2.30 × 10(-20)≤P≤2.41 × 10(-7)) and identified three new susceptibility loci: 4q24 (NFKB1) at rs1020760 (P=2.19 × 10(-8)), 12p13.3 (CD27-LAG3) at rs758739 (P=4.08 × 10(-8)) and 17q12 (IKZF3) at rs10852936 (P=1.96 × 10(-8)).
The subunit of IL-23 (IL12B) and its receptor (IL23R) gene single-nucleotide polymorphisms (SNPs) have been shown to be associated with several autoimmune diseases such as inflammatory bowel disease, psoriasis and ankylosing spondylitis.
This study aims to assess whether the association between the non-susceptibility allelic variants of IL12B single-nucleotide polymorphism (SNPs) rs3212227 and rs6887695, IL23R SNPs rs11209026 and rs7530511, IL6 SNP rs1800795 and HLA-Cw6 could be correlated with decreased risk for psoriasis.
We genotyped 142 patients and 160 healthy volunteers to evaluate the possible relationship between susceptibility to psoriasis and the HLA-C*0602 allele and polymorphisms in the TNF, IL12B, and IL23R genes.
Our study showed significant associations between psoriasis and both IL12B gene SNPs, rs3212227 (odds ratio (OR) = 1.35, P = 4.94E-04) and rs6887695 (OR = 1.32, P = 2.00E-03), but no significant association between psoriasis and the IL23R SNP, rs11209026.
Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B(∗)52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor.
The genetic polymorphism of the IL-12B gene (rs6887695) may be associated with the psoriasis susceptibility in the Chinese Han population, especially for the plaque cases, but not associated with the age at onset, family history, or sex.
Here, we demonstrate that a psoriasis-associated risk haplotype at the IL12B locus leads to increased expression of IL12B by monocytes and correlated with increased serum levels of IL-12, IFN-γ and the IFN-γ induced chemokine, CXCL10.