Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis 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).