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

https://doi.org/10.1016/j.jdermsci.2014.05.010Get rights and content

Highlights

  • 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.

Abstract

Background

Common 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.

Objective

To analyze the effect of single nucleotide polymorphisms (SNPs) previously linked to Ps (IL12B rs6887695 and rs3212227, IL23R rs2201841 and rs11209026, and IL23A rs2066808) in the main phenotype and metabolic/cardiovascular characteristics among Ps patients from a Northern Spanish population.

Methods

The 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.

Results

An 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).

Conclusion

In 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.

Section snippets

Introductions

Genome-wide association studies (GWAs) has led to important advances in the discovery of gene variants implicated in the risk of developing Psoriasis (Ps, MIM 177,900) and psoriatic arthritis (PsA, MIM 607,507). Among others, single-nucleotide polymorphisms (SNPs) in IL-23R, IL-12B and IL23A have been linked to Ps and PsA susceptibility [1], [2], [3], [4], [5], [6], [7], [8]. IL12B, which encodes the p40 subunit of IL12 and IL23, was among the first genes outside the HLA linked to Ps in

Material and methods

Patients were unrelated Caucasians from the region of Asturias (Northern Spain, total population 1 million) recruited through the dermatology department of the Hospital Universitario Central de Asturias. Written informed consent was obtained from each participant, under the protocol approved by our Ethical Committee. Controls were healthy subjects from the same population, matched to patients for age and gender. They were recruited through our blood bank, selecting healthy individuals without

Results

The main characteristics of patients are summarized in Table 1. Absolute values and frequencies for genotype and alleles of the five SNPs in controls, Ps patients and PsA subgroups are shown in Table 2. Genotype frequencies did not deviate from the expected under the Hardy–Weinberg equilibrium in both, patients and controls (p < 0.05).

We found a significant association between the IL12B rs6887695 and Ps (p < 0.01, OR = 1.50, 95% CI = 1.14–1.97) (Table 2). The rs6887695-GG risk genotype was

Discussion

Common variant SNPs of IL-23R, IL-12B and IL23A have been associated to increased Ps susceptibility in several populations. Previously, we had been able to replicate the IL12B rs6887695-GG genotype association to Ps described by several authors [7], [9], [23]. Data from the minor allele frequency variants of IL12B rs6887695 (C) and rs3212227 (C) was in agreement with other studies [2], [9], [24], including a recent meta-analysis of IL12B polymorphisms in Ps and PsA that estimated an OR < 2 for

Acknowledgement

Part of this study was supported by a research grant from Janssen-Cilag.

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    Present address: Dermatology Department, Hospital de León (C/Altos de Nava s/n, 24071, León, Spain. Tel.: +34 987 23 74 00).

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