溃疡性结肠炎细胞周期蛋白依赖性激酶抑制因子2B反义RNA 1基因多态性和单倍型分析

doi:10.3760/cma.j.cn311367-20220404-00149

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题名	溃疡性结肠炎细胞周期蛋白依赖性激酶抑制因子2B反义RNA 1基因多态性和单倍型分析
其他题名	Analysis of the polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene in patients with ulcerative colitis
作者	徐缘; 邵晓晓; 胡定元; 饶舜禹; 肖慧盈; 方晔; 蒋益
发表日期	2022
发表期刊	中华消化杂志影响因子和分区
语种	中文
原始文献类型	Periodical
关键词	细胞周期蛋白依赖性激酶抑制因子2B-AS1 结肠炎，溃疡性多态性，单核苷酸单倍型
其他关键词	CDKN2B-AS1 ; Colitis, ulcerative ; Polymorphism, single nucleotide ; Haplotypes
摘要	目的:探讨细胞周期蛋白依赖性激酶抑制因子2B反义RNA 1( CDKN2 B- AS1)基因多态性及其单倍型与溃疡性结肠炎(UC)发病风险的关系。方法:选择2012年1月至2021年1月温州医科大学附属第二医院(育英儿童医院)消化内科确诊的534例UC患者，以及同期性别、年龄相匹配的560名健康对照者。采用基质辅助激光解吸电离-飞行时间质谱技术检测静脉血 CDKN2 B- AS1(rs1063192、rs10757274、rs10757278、rs1333048、rs2383207)的基因型。采用非条件logistic回归分析UC患者与健康对照者 CDKN2 B- AS1基因多态性的分布差异，以及对UC临床病理特征的影响。应用Haploview 4.2软件进行连锁不平衡和单倍型分析。采用卡方检验进行统计学比较。结果:UC患者rs1063192的变异基因型AG+GG和变异等位基因G的频率均高于健康对照者[32.4%(173/534)比24.8%(139/560)、18.1%(193/1 068)比13.7%(153/1 120)]，差异均有统计学意义[ OR＝1.45、1.40，95%置信区间(95% CI) 1.12~1.89、1.11~1.77， P＝0.006、0.004，校正 P＝0.030、0.020]。UC患者rs10757274的变异等位基因G的频率低于健康对照者[34.7%(371/1 068)比39.5%(442/1 120)]，差异有统计学意义( OR＝0.82，95% CI 0.69~0.98， P＝0.025)，但经Bonferroni法校正后，差异无统计学意义(校正 P0.05)。蒙特利尔分型为广泛结肠炎的患者rs1063192的纯合子变异基因型GG的频率高于直肠炎+左半结肠炎患者[6.6%(14/211)比1.9%(6/323)]，差异有统计学意义( OR＝3.92，95% CI 1.47~10.42， P＝0.006，校正 P＝0.030)。 CDKN2 B- AS1基因的rs10757274、rs2383207、rs10757278和rs1333048彼此存在连锁不平衡关系。UC患者单倍型GGGC的频率低于健康对照者[33.3%(355.5/1 068)比37.8%(423.4/1 120)]，而单倍型AGGC的频率高于健康对照者[6.7%(71.7/1 068)比3.6%(40.3/1 120)]，差异均有统计学意义( χ2＝4.81、11.16， P＝0.028、<0.001)。结论:CDKN2 B- AS1基因的rs1063192变异可能增加UC发病风险，其纯合子变异基因型GG携带者发生广泛结肠炎的风险可能增高。由rs10757274、rs2383207、rs10757278、rs1333048构成的单倍型中，携带单倍型GGGC可能降低UC发病风险，而携带单倍型AGGC可能增加UC发病风险。rs10757274变异与UC发病风险的相关性仍需扩大样本量进一步验证。
其他摘要	Objective:To investigate the relationship between polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 ( CDKN2 B- AS1) gene and the risk of ulcerative colitis (UC). Methods:From January 2012 to January 2021, a total of 534 UC patients diagnosed at the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University (Yuying Children′s Hospital) and during the same period 560 gender- and age-matched healthy controls were selected. Genotypes of CDKN2 B- AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) in venous blood were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression was used to analyze the difference in the distribution of CDKN2 B- AS1 gene polymorphisms between UC patients and healthy controls, as well as the influence on the clinicopathologic characteristics of UC patients. Software Haploview 4.2 was used to analyze the linkage disequilibrium and haplotype. Chi-square test was used for statistical analysis. Results:The frequencies of variant genotype (AG+ GG) and variant allele (G) of rs1063192 in UC patients were higher than those in healthy controls (32.4%, 173/534 vs. 24.8%, 139/560; 18.1%, 193/1 068 vs. 13.7%, 153/1 120), and the differences were statistically significant ( OR=1.45 and 1.40, 95% confidence interval(95% CI) 1.12 to 1.89 and 1.11 to 1.77, P=0.006 and 0.004, corrected P=0.030 and 0.020). The frequency of variant allele (G) of rs10757274 in UC patients was lower than that in healthy controls (34.7%, 371/1 068 vs. 39.5%, 442/1 120), and the difference was statistically significant ( OR=0.82, 95% CI 0.69 to 0.98, P=0.025). However, the difference was not significant after Bonferroni correction (corrected P0.05). According to the Montreal classification, the frequency of homozygous variant genotype (GG) of rs1063192 in the patients with extensive colitis was higher than that in patients with proctitis plus left-sided colitis (6.6%, 14/211 vs. 1.9%, 6/323), and the difference was statistically significant ( OR=3.92, 95% CI 1.47 to 10.42, P=0.006, corrected P=0.030). There was linkage disequilibrium among rs10757274, rs2383207, rs10757278 and rs1333048 of CDKN2 B- AS1 gene. The frequency of haplotype GGGC in UC patients was lower than that in healthy controls (33.3%, 355.5/1 068 vs. 37.8%, 423.4/1 120), and the frequency of haplotype AGGC in UC patients was higher than that in healthy controls (6.7%, 71.7/1 068 vs. 3.6%, 40.3/1 120), and the differences were statistically significant ( χ2=4.81 and 11.16, P=0.028 and<0.001). Conclusions:The variation of rs1063192 in CDKN2 B- AS1 gene may increase the risk of UC. The risk of extensive colitis in patients carrying homozygous variant genotype (GG) of rs1063192 may rise. Among the haplotypes composed of rs10757274, rs2383207, rs10757278 and rs1333048, the risk of UC may decrease in the individuals carrying haplotype GGGC. However, the risk of UC may increase in the individuals carrying haplotype AGGC. The correlation between the variation of 10757274 and the risk of UC still needs to be further verified by expanding the sample size.
资助项目	浙江省医药卫生科技计划（2021KY802,2021KY803）;浙江省中医药科技计划（2019ZB075）;温州市科技计划（Y20190603）;贺林院士工作站科研基金（19331101）
ISSN	0254-1432
卷号	42 期号:9 页码:627-633
DOI	10.3760/cma.j.cn311367-20220404-00149
页数	7
收录类别	ISTIC ; CNKI ; 维普 ; 北大核心 ; CSCD ; 万方
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引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/166464
专题	第二临床医学院，附属第二医院、育英儿童医院_内科学_消化内科
作者单位	温州医科大学附属第二医院(育英儿童医院)消化内科，温州　325000
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院_内科学_消化内科
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院_内科学_消化内科
推荐引用方式 GB/T 7714	徐缘,邵晓晓,胡定元,等. 溃疡性结肠炎细胞周期蛋白依赖性激酶抑制因子2B反义RNA 1基因多态性和单倍型分析[J]. 中华消化杂志,2022,42(9):627-633.
APA	徐缘., 邵晓晓., 胡定元., 饶舜禹., 肖慧盈., ... & 蒋益. (2022). 溃疡性结肠炎细胞周期蛋白依赖性激酶抑制因子2B反义RNA 1基因多态性和单倍型分析. 中华消化杂志, 42(9), 627-633.
MLA	徐缘,et al."溃疡性结肠炎细胞周期蛋白依赖性激酶抑制因子2B反义RNA 1基因多态性和单倍型分析".中华消化杂志 42.9(2022):627-633.