Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus

• Genetic variation at the IL12/23 pathway is studied in Spanish psoriasis patients.
• Single nucleotide polymorphisms in IL12/23 genes influence psoriasis phenotype.
• The common variant of IL23R rs11209026 (G) increases psoriasis severity.
• IL23A rs2066808 common risk variant (A) associates to coexistence of arthritis.
• Minor variants of IL12B and IL23R are associated to diabetes mellitus type 2.

BackgroundCommon DNA variants in IL12B, IL23R and IL23A have been associated with an increased susceptibility to psoriasis (Ps) and psoriatic arthritis (PsA). Metabolic comorbidities and cardiovascular risk factors have also been associated to both Ps and PsA.ObjectiveTo analyze the effect of single nucleotide polymorphisms (SNPs) previously linked to Ps (IL12B rs6887695 and rs3212227, IL23R rs2201841 and rs11209026, and IL23Ars2066808) in the main phenotype and metabolic/cardiovascular characteristics among Ps patients from a Northern Spanish population.MethodsThe aforementioned genetic variants were determined in a total of 405 chronic plaque Ps patients and 426 controls. Subsequent statistical analysis included stratification for psoriatic clinical characteristics (age of onset, disease severity, familial psoriasis, HLA-Cw6, nail psoriasis) plus diabetes mellitus type 2, arterial hypertension, dyslipidemia and ischemic cardiac events as comorbidities.ResultsAn association between IL23R rs11209026-GG genotype with a more severe disease (p = 0.02, OR = 2.11, 95% CI = 1.13–3.95). Carriers of the IL23A rs2066808-A allele were significantly more frequent among PsA patients (p = 0.016, OR =  3.04, 95% CI = 1.19–7.78). We found significant associations between three SNP genotypes and type 2 diabetes: IL12B rs6887695-CC (p = 0.03, OR = 2.90, 95% CI = 1.09–7.69), IL12B rs3212227-CC (p = 0.035, OR = 5.90, 95% CI =  1.35–25.73) and IL23R rs2201841-GG (p =  0.027, OR = 2.69, 95% CI = 1.09–6.66).ConclusionIn our population, genetic variation at IL12B, IL23R and IL23A has an influence not only on the risk for Ps but also on disease severity and type 2 diabetes mellitus.