有机阳离子转运体基因（OCTN）和IBD5与溃疡性结肠炎关联的证据。
Evidence for association of OCTN genes and IBD5 with ulcerative colitis.
作者信息
Waller S, Tremelling M, Bredin F, Godfrey L, Howson J, Parkes M
机构信息
IBD Researcg Group, Department of Medicine, University of Cambridge, Cambridge, UK.
出版信息
Gut. 2006 Jun;55(6):809-14. doi: 10.1136/gut.2005.084574. Epub 2005 Dec 16.
BACKGROUND AND AIMS
Genetic association between Crohn's disease (CD) and OCTN1 (SLC22A4) C1672T/OCTN2 (SLC22A5) G-207C variants in IBD5 has recently been reported. These genes encode solute carriers and the association was suggested to be distinct from the background IBD5 risk haplotype. There have been conflicting reports of the association between markers in the IBD5 region and ulcerative colitis (UC) and interaction (epistasis) between this locus and CARD15. Our aim was to ascertain the contribution of OCTN variants to UC and CD in a large independent UK dataset, to seek genetic evidence that the OCTN association is distinct from the IBD5 risk haplotype and to identify interactions between the IBD5 and CARD15 loci.
METHODS
A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN2-207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096. Data were analysed by logistic regression methods within STATA.
RESULTS
OCTN variants were as strongly associated with UC and IBD overall as they were with CD (p = 0.0001; OR 1.3 (95% confidence interval 1.1-1.5)). OCTN variants were in tight linkage disequilibrium with the extended IBD5 risk haplotype D' 0.79 and 0.88, and r2 = 0.62 and 0.72 for IGR2096 and 3096, respectively. There was no deviation from a multiplicative model of interaction between CARD15 and IBD5 on the penetrance scale.
CONCLUSIONS
The OCTN variants were associated with susceptibility to IBD overall. The effect was equally strong in UC and CD. Although OCTN variants may account for the increased risk of IBD associated with IBD5, a role for other candidate genes within this extended haplotype was not excluded. There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD.
背景与目的
最近有报道称，克罗恩病（CD）与炎症性肠病5（IBD5）区域中的OCTN1（溶质载体家族22成员4，SLC22A4）基因C1672T变异及OCTN2（溶质载体家族22成员5，SLC22A5）基因G - 207C变异之间存在基因关联。这些基因编码溶质载体，且该关联被认为与背景IBD5风险单倍型不同。关于IBD5区域标记与溃疡性结肠炎（UC）之间的关联以及该基因座与CARD15之间的相互作用（上位性），一直存在相互矛盾的报道。我们的目的是在一个大型独立的英国数据集中确定OCTN变异对UC和CD的影响，寻找基因证据以证明OCTN关联与IBD5风险单倍型不同，并确定IBD5和CARD15基因座之间的相互作用。
方法
对总共1104名无关的患有炎症性肠病（IBD）的白种人受试者（496例CD、512例UC、96例未定型）以及750名种族匹配的对照，进行与CD相关基因（OCTN1 + 1672、OCTN2 - 207和IGR2230）中的三个单核苷酸多态性（SNP）以及两个侧翼IBD5标签SNP（IGR2096和IGR3096）的基因分型。在STATA软件中通过逻辑回归方法对数据进行分析。
结果
OCTN变异与UC和整体IBD的关联程度与CD相同（p = 0.0001；比值比1.3（95%置信区间1.1 - 1.5））。OCTN变异与扩展的IBD5风险单倍型紧密连锁不平衡，D'值分别为0.79和0.88，IGR2096和IGR3096的r2值分别为0.62和0.72。在发病风险尺度上，CARD15与IBD5之间的相互作用不存在偏离相乘模型的情况。
结论
OCTN变异总体上与IBD易感性相关。在UC和CD中，该效应同样强烈。尽管OCTN变异可能解释了与IBD5相关的IBD风险增加，但并不排除该扩展单倍型内其他候选基因的作用。在IBD易感性方面，没有统计学证据表明CARD15与OCTN或IBD5变异之间存在相互作用。
Zotero 插件