IBD Genetics Research Unit, Department of Gastroenterology, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
Inflamm Bowel Dis. 2011 Jun;17(6):1387-91. doi: 10.1002/ibd.21499. Epub 2010 Oct 25.
NLRP3 (formerly known as CIAS1 or NALP3) encodes a key component of the inflammasome and is a strong candidate gene for Crohn's disease (CD) susceptibility. A recent study reported significant and internally replicated association between CD and six single nucleotide polymorphisms (SNPs) in a regulatory region 5.3 kb downstream of NLRP3. Independent replication is required to verify these findings.
In all, 1298 CD cases and 1244 healthy controls were genotyped for the six SNPs using Taqman. Single locus, haplotype, and subphenotype analyses were conducted using logistic regression-based methods and PLINK, respectively.
No significant associations were found, either on single locus, subphenotype, or haplotype analysis.
Given our high (>90%) power to replicate findings from the index study, our data suggest either a much smaller effect size for the association between NLRP3 and CD susceptibility than previously reported or the possibility of a false-positive result in the index study. Further studies in other populations are required to determine what role, if any, NLRP3 variants play in CD susceptibility.
NLRP3（以前称为 CIAS1 或 NALP3）编码炎症小体的关键组成部分，是克罗恩病（CD）易感性的候选基因。最近的一项研究报告称，在 NLRP3 下游 5.3kb 的调控区域中，CD 与六个单核苷酸多态性（SNP）之间存在显著的、内部复制的关联。需要进行独立复制来验证这些发现。
共对 1298 例 CD 病例和 1244 例健康对照进行了 NLRP3 下游 5.3kb 调控区域的六个 SNP 的 Taqman 基因分型。使用基于逻辑回归的方法和 PLINK 分别进行单基因座、单倍型和亚表型分析。
无论是在单基因座、亚表型还是单倍型分析中，均未发现显著相关性。
鉴于我们有很高（>90%）的能力复制索引研究中的发现，我们的数据表明，NLRP3 与 CD 易感性之间的关联效应大小比之前报道的要小得多，或者索引研究中存在假阳性结果的可能性。需要在其他人群中进行进一步的研究，以确定 NLRP3 变异体在 CD 易感性中起何种作用（如果有的话）。
