Li Yonghong, Liao Wilson, Chang Monica, Schrodi Steven J, Bui Nam, Catanese Joseph J, Poon Annie, Matsunami Nori, Callis-Duffin Kristina P, Leppert Mark F, Bowcock Anne M, Kwok Pui-Yan, Krueger Gerald G, Begovich Ann B
Celera, Alameda, California 94502, USA.
J Invest Dermatol. 2009 Mar;129(3):629-34. doi: 10.1038/jid.2008.297. Epub 2008 Oct 16.
Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B, and IL23R, and although other psoriasis-associated variants have been identified, incontrovertible statistical evidence for these markers has not yet been obtained. To help resolve this issue, we tested 15 single-nucleotide polymorphisms (SNPs) from 7 putative psoriasis-risk genes in 1,448 psoriasis patients and 1,385 control subjects; 3 SNPs, rs597980 in ADAM33, rs6908425 in CDKAL1 and rs3789604 in PTPN22, were significant with the same risk allele as in prior reports (one-sided P<0.05, false discovery rate<0.15). These three markers were tested in a fourth sample set (599 cases and 299 controls); one marker, rs597980, replicated (one-sided P<0.05) and the other two had odds ratios with the same directionality as in the original sample sets. Mantel-Haenszel meta-analyses of all available case-control data, including those published by other groups, showed that these three markers were highly significant (rs597980: P=0.0057 (2,025 cases and 1,597 controls), rs6908425: P=1.57 x 10(-5) (3,206 cases and 4,529 controls), and rs3789604: P=3.45 x 10(-5) (2,823 cases and 4,066 controls)). These data increase the likelihood that ADAM33, CDKAL1, and PTPN22 are true psoriasis-risk genes.
已知银屑病的易感性受HLA - C、IL12B和IL23R基因变异的影响，尽管已鉴定出其他与银屑病相关的变异，但尚未获得这些标记物的确凿统计证据。为帮助解决这一问题，我们在1448例银屑病患者和1385例对照受试者中检测了来自7个假定的银屑病风险基因的15个单核苷酸多态性（SNP）；3个SNP，即ADAM33基因中的rs597980、CDKAL1基因中的rs6908425和PTPN22基因中的rs3789604，与先前报告中的风险等位基因相同且具有显著性（单侧P<0.05，错误发现率<0.15）。在第四个样本集（599例病例和299例对照）中对这三个标记物进行了检测；其中一个标记物rs597980得到重复验证（单侧P<0.05），另外两个标记物的优势比方向与原始样本集相同。对所有可用的病例对照数据（包括其他研究小组发表的数据）进行Mantel - Haenszel荟萃分析表明，这三个标记物具有高度显著性（rs597980：P = 0.0057（2025例病例和1597例对照），rs6908425：P = 1.57×10⁻⁵（3206例病例和4529例对照），rs3789604：P = 3.45×10⁻⁵（2823例病例和4066例对照））。这些数据增加了ADAM33、CDKAL1和PTPN22是真正的银屑病风险基因的可能性。
