Nair Rajan P, Ruether Andreas, Stuart Philip E, Jenisch Stefan, Tejasvi Trilokraj, Hiremagalore Ravi, Schreiber Stefan, Kabelitz Dieter, Lim Henry W, Voorhees John J, Christophers Enno, Elder James T, Weichenthal Michael
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0932, USA.
J Invest Dermatol. 2008 Jul;128(7):1653-61. doi: 10.1038/sj.jid.5701255. Epub 2008 Jan 24.
Psoriasis is a common inflammatory and hyperproliferative skin disease with a multifactorial genetic basis. A recent study reported that psoriasis was associated with the IL12B haplotype rs3212227 (3'-untranslated region)-rs6887695 (60 kb, 5') and the IL23R haplotype rs7530511 (L310P)-rs11209026 (Q381R). We examined these four single-nucleotide polymorphisms (SNPs) for association with psoriasis in two groups of North American and German Caucasians: (1) 1,810 cases and 2,522 controls; and (2) 509 pedigrees. Both IL12B markers showed highly significant association with psoriasis in the case-control (rs3212227, odds ratio (OR)=1.62, P=1.7 x 10(-15); rs6887695, OR=1.49, P=2.7 x 10(-15)) and in the family-based analysis (rs3212227, P=2.2 x 10(-3); rs6887695, P=1.7 x 10(-3)). The IL23R SNPs also showed significant association in the cases and controls (rs7530511, OR=1.22, P=3.9 x 10(-3); rs11209026, OR=1.40, P=3.8 x 10(-4)). For both genes, common risk haplotypes were identified whose statistical significance approached (IL23R) or exceeded (IL12B) genome-wide criteria. We found no statistical evidence for interactions of these haplotypes with HLA-Cw6. Our results confirm associations between IL12B and IL23R and psoriasis in Caucasians, and provide a genetic basis for the clinical association between psoriasis and Crohn's disease.
银屑病是一种常见的具有多因素遗传基础的炎症性和增殖性皮肤病。最近一项研究报告称，银屑病与IL12B单倍型rs3212227（3'-非翻译区）-rs6887695（60 kb，5'）以及IL23R单倍型rs7530511（L310P）-rs11209026（Q381R）相关。我们在两组北美和德国白种人中检测了这四个单核苷酸多态性（SNP）与银屑病的关联：（1）1810例病例和2522例对照；（2）509个家系。在病例对照研究中，两个IL12B标记与银屑病均显示出高度显著的关联（rs3212227，优势比（OR）=1.62，P = 1.7×10⁻¹⁵；rs6887695，OR = 1.49，P = 2.7×10⁻¹⁵），在基于家系的分析中也是如此（rs3212227，P = 2.2×10⁻³；rs6887695，P = 1.7×10⁻³）。IL23R SNP在病例和对照中也显示出显著关联（rs7530511，OR = 1.22，P = 3.9×10⁻³；rs11209026，OR = 1.40，P = 3.8×10⁻⁴）。对于这两个基因，均鉴定出了常见的风险单倍型，其统计学显著性接近（IL23R）或超过（IL12B）全基因组标准。我们没有发现这些单倍型与HLA - Cw6相互作用的统计学证据。我们的结果证实了白种人中IL12B和IL23R与银屑病之间的关联，并为银屑病与克罗恩病之间的临床关联提供了遗传基础。
