*Institute for Digestive Research and †Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania; ‡Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany; §Center of Hepatology, Gastroenterology and Dietetics, Vilnius University, Vilnius, Lithuania; ¶Digestive Diseases Centre GASTRO, Riga, Latvia; Departments of ‖Children Diseases and **Health Management, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania; ††Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; ‡‡Medical Department, Hospital of Southern Jutland, Aabenraa, Denmark; §§Internal Disease Department, Riga Stradins University, Riga, Latvia; and ¶¶Department of Surgery, Academy of Medicine, Lithuanian University of Health Science, Kaunas, Lithuania.
Inflamm Bowel Dis. 2013 Oct;19(11):2349-55. doi: 10.1097/MIB.0b013e3182a3eaeb.
Differences between populations might be reflected in their different genetic risk maps to complex diseases, for example, inflammatory bowel disease. We here investigated the role of known inflammatory bowel disease-associated single nucleotide polymorphisms (SNPs) in a subset of patients with ulcerative colitis (UC) from the Northeastern European countries Lithuania and Latvia and evaluated possible epistatic interactions between these genetic variants.
We investigated 77 SNPs derived from 5 previously published genome-wide association studies for Crohn's disease and UC. Our study panel comprised 444 Lithuanian and Latvian patients with UC and 1154 healthy controls. Single marker case-control association and SNP-SNP epistasis analyses were performed.
We found 14 SNPs tagging 9 loci, including 21q21.1, NKX2-3, MST1, the HLA region, 1p36.13, IL10, JAK2, ORMDL3, and IL23R, to be associated with UC. Interestingly, the association of UC with previously identified variants in the HLA region was not the strongest association in our study (P = 4.34 × 10, odds ratio [OR] = 1.25), which is in contrast to all previously published studies. No association with any disease subphenotype was found. SNP-SNP interaction analysis showed significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes and increased risk for UC (P = 1.64 × 10, OR = 2.44). The association has been confirmed in the Danish study group (P = 0.04, OR = 3.25).
We confirmed the association of the 9 loci (21q21.1, 1p36.13, NKX2-3, MST1, the HLA region, IL10, JAK2, ORMDL3, and IL23R) with UC in the Lithuanian-Latvian population. SNP-SNP interaction analyses showed that the combination of SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk for UC.
人群之间的差异可能反映在他们对复杂疾病（例如炎症性肠病）的不同遗传风险图谱上。在这里，我们研究了已发现的与炎症性肠病相关的单核苷酸多态性（SNP）在来自北欧国家立陶宛和拉脱维亚的一部分溃疡性结肠炎（UC）患者中的作用，并评估了这些遗传变异之间可能存在的上位性相互作用。
我们研究了来自 5 项先前发表的克罗恩病和 UC 全基因组关联研究的 77 个 SNP。我们的研究小组包括 444 名立陶宛和拉脱维亚 UC 患者和 1154 名健康对照者。进行了单标记病例对照关联和 SNP-SNP 上位性分析。
我们发现 14 个 SNP 标记了 9 个位点，包括 21q21.1、NKX2-3、MST1、HLA 区域、1p36.13、IL10、JAK2、ORMDL3 和 IL23R，与 UC 相关。有趣的是，与先前在 HLA 区域中发现的 UC 相关变异的关联在我们的研究中并不是最强的关联（P=4.34×10，优势比[OR]=1.25），这与所有先前发表的研究相反。没有发现与任何疾病亚表型的关联。SNP-SNP 相互作用分析显示，PTPN22（rs2476601）和 C13orf31（rs3764147）基因中的 SNP 之间存在显著的上位性，并且 UC 的风险增加（P=1.64×10，OR=2.44）。这一关联在丹麦研究组中得到了证实（P=0.04，OR=3.25）。
我们在立陶宛-拉脱维亚人群中证实了 9 个位点（21q21.1、1p36.13、NKX2-3、MST1、HLA 区域、IL10、JAK2、ORMDL3 和 IL23R）与 UC 的关联。SNP-SNP 相互作用分析表明，PTPN22（rs2476601）和 C13orf31（rs3764147）基因中的 SNP 组合增加了 UC 的风险。
