Department of Gastroenterology, Asan Medical Center, Seoul, South Korea.
Inflamm Bowel Dis. 2013 Apr;19(5):954-66. doi: 10.1097/MIB.0b013e3182802ab6.
BACKGROUND: Recent genome-wide association studies and meta-analyses have identified 47 susceptibility loci for ulcerative colitis (UC) in Caucasian populations. A previous genome-wide association study of UC in a Japanese population suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. We performed a genome-wide association studies to identify UC susceptibility loci in a Korean population and further comparative study. METHODS: We analyzed 581,060 autosomal single-nucleotide polymorphisms (SNPs) in 388 individuals with UC and 739 control subjects in the discovery stage. For the validation, 64 suggestive SNPs were analyzed in an additional 417 affected individuals and 732 control subjects. RESULTS: Three genetic loci were validated for significant association, and all were previously reported in Caucasians including the major histocompatibility complex region (top SNP, rs9271366; P = 1.03 × 10(-18), odds ratio [OR] = 2.10), 16q24.1 (rs16940186; P = 4.39 × 10(-10), OR = 1.56), and RNF186-OTUD3-PLA2G2E at chromosome arm 1p36.13 (top SNP, rs4654903 in OTUD3; P = 7.43 × 10(-9), OR = 0.64). Although failed to reach genome-wide statistical significance, 2 additional loci previously reported in Caucasians including rs17085007 at chromosome arm 13q12 and JAK2 at chromosome arm 9p24 were significant after Bonferroni correction (P(corrected) = 0.0016 and P(corrected) = 0.0056, respectively). FOS, UBE2L3, the JAK2 gene region, and rs1297265 at chromosome arm 21q21.1 likely play a role in both Crohn's disease and UC. CONCLUSIONS: Our data support the biologic significance of the overlapping loci for UC between Caucasian and Korean populations. Our data suggest that genetic associations for UC tend to overlap more extensively among different ethnic groups than those for Crohn's disease, which shows well-established dependence on ethnicity.
背景:最近的全基因组关联研究和荟萃分析已经确定了 47 个溃疡性结肠炎(UC)易感性位点在白种人群体中。之前对日本人群的 UC 全基因组关联研究表明,白种人和亚洲人群的易感性位点存在边缘共享。我们进行了全基因组关联研究,以确定韩国人群中的 UC 易感性位点,并进一步进行了比较研究。
方法:我们在发现阶段分析了 388 名 UC 患者和 739 名对照个体的 581,060 个常染色体单核苷酸多态性(SNP)。在验证阶段,在另外的 417 名受影响个体和 732 名对照个体中分析了 64 个提示性 SNP。
结果:三个遗传位点被验证为显著关联,并且都在白种人中被报道过,包括主要组织相容性复合体区域(最高 SNP,rs9271366;P=1.03×10(-18),比值比[OR] = 2.10)、16q24.1(rs16940186;P=4.39×10(-10),OR = 1.56)和染色体臂 1p36.13 上的 RNF186-OTUD3-PLA2G2E(最高 SNP,OTUD3 中的 rs4654903;P=7.43×10(-9),OR = 0.64)。虽然没有达到全基因组统计学意义,但白种人中以前报道的另外两个位点,包括染色体臂 13q12 上的 rs17085007 和染色体臂 9p24 上的 JAK2,在 Bonferroni 校正后是显著的(P(corrected)=0.0016 和 P(corrected)=0.0056,分别)。FOS、UBE2L3、JAK2 基因区域和染色体臂 21q21.1 上的 rs1297265 可能在克罗恩病和 UC 中都有作用。
结论:我们的数据支持白种人和韩国人群之间 UC 重叠位点的生物学意义。我们的数据表明,UC 的遗传关联在不同种族群体之间比克罗恩病更广泛地重叠,而后者明显依赖于种族。
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