Association of fucosyltransferase 2 gene variants with ulcerative colitis in Han and Uyghur patients in China
Association of fucosyltransferase 2 gene variants with ulcerative colitis in Han and Uyghur patients in China
复制标题
岩藻糖基转移酶2基因变异与中国汉族和维吾尔族患者溃疡性结肠炎的相关性
DOI：
10.3748/wjg.v18.i34.4758
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发表时间：
2012-09-14
影响因子：
4.3
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Aheman, Ayinuer;Luo, He-Sheng;Gao, Feng
目的：探讨聚焦转移酶2 （FUT2）变异对新疆汉族和维吾尔族溃疡性结肠炎（UC）遗传易感性和临床异质性的影响。方法：2010年1月至2011年5月在中国新疆人民医院共纳入102例UC患者（53例汉族患者，男22例，女31例；49例维吾尔族患者，男25例，女24例；年龄48 ~ 16岁）和310例年龄和性别匹配的健康对照。UC的诊断基于临床，内镜和组织学结果，并遵循Lennard-Jones标准。采集血样，按常规实验室方法提取基因组DNA。采用基于聚合酶链反应序列的分型方法鉴定FUT2变异rs281377、rs1047781、rs601338和rs602662。记录并比较UC患者与健康对照之间的基因型和等位基因频率。还比较了汉族和维吾尔族患者的基因型频率。研究了汉族和维吾尔族患者之间遗传变异与UC的潜在关联。结果：与对照组相比，汉族人群中rs281377与UC显著相关（P = 0.011），而维吾尔族人群中rs281377与UC无相关性（P = 0.06）。UC组的TT纯合rs281377频率高于对照组（88.7% vs 68.7%, 55.1% vs 50.3%）。rs1047781在维吾尔族人群中与UC特异性相关（P = 0.001），但在汉族人群中与UC无关（P = 0.13）。UC组TT纯合子rs1047781频率低于对照组（9.5% vs 11.8%, 4.0% vs 6.7%）。rs601338在两种人群中与UC相关（汉族，P = 0.025；维吾尔族，P = 8.33 × 10(-5)）。UC组AA纯合子rs601338频率低于对照组（0% vs 1.8%, 12.2% vs 13.4%）。在汉族和维吾尔族人群中均未发现rs602662与UC存在关联。等位基因分析显示，与对照相比，rs281377等位基因与汉族人群UC有显著相关性[P = 0.001, OR = 0.26]，而与维吾尔族人群UC无相关性（P = 0.603, OR = 1.14），与维吾尔族人群UC有相关性（P = 0.001, OR = 0.029），与汉族人群UC无相关性（P = 0.074, OR = 0.62）。此外，rs601338在汉族（P = 0.005, OR = 0.1）和维吾尔族（P = 0.002, OR = 0.43）人群中都与UC相关。Meta分析显示，与对照组相比，rs1047781和rs601338可增加UC的风险[P = 0.005, OR = 0.47；P = 0.0003, or = 0.35；95%可信区间（CI）分别为0.31-0.72和0.21-0.58]，但rs281377和rs602662在UC患者与对照组之间差异无统计学意义（P = 0.10, OR = 0.71; P = 0.68, OR = 0.09； 95% CI分别为0.47-1.07和0.56-1.47）。结论：功能相关的FUT2基因变异与UC相关，提示其在UC的发病机制中发挥潜在作用，并可能导致汉族和维吾尔族UC患者的临床异质性。(C) 2012年白石登。版权所有。
AIM: To investigate the contribution of fucosyltransferase 2 (FUT2) variants to the genetic susceptibility and clinical heterogeneity of ulcerative colitis (UC) between Han and Uyghur patients in Xinjiang, China.METHODS: A total of 102 UC patients (53 Han patients including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48 16 years) and 310 age- and sex-matched healthy controls were enrolled from January 2010 to May 2011 in Xinjiang People's Hospital of China. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by the routine laboratory methods. Polymerase chain reaction-sequence-based typing method was used to identify FUT2 variants rs281377, rs1047781, rs601338 and rs602662. Genotypic and allelic frequencies were documented and compared between the UC patients and the healthy controls. Genotypic frequencies were also compared between Han and Uyghur patients. Potential association of genetic variation and UC between Han and Uyghur patients was examined.RESULTS: rs281377 was found significantly associated with UC in the Han population as compared with the controls (P = 0.011) while rs281377 was not associated with UC in the Uyghur population (P = 0.06). TT homozygous rs281377 frequencies were higher in the UC groups than in the controls (88.7% vs 68.7% and 55.1% vs 50.3%). rs1047781 was specifically associated with UC in the Uyghur population (P = 0.001), but not associated with UC in the Han population (P = 0.13). TT homozygous rs1047781 frequencies were lower in the UC groups than in the controls (9.5% vs 11.8% and 4.0% vs 6.7%). rs601338 was statistically related to UC in both populations (Han, P = 0.025; Uyghur, P = 8.33 x 10(-5)). AA homozygous rs601338 frequencies were lower in the UC groups than in the controls (0% vs 1.8% and 12.2% vs 13.4%). No association was found between rs602662 and UC in both Han and the Uyghur populations. Allelic analysis showed that rs281377 allele was significantly associated with UC in the Han population as compared with the controls [P = 0.001, odd ratio (OR) = 0.26], however, it was not associated with UC in the Uyghur population (P = 0.603, OR = 1.14), and rs1047781 allele was associated with UC in the Uyghur population (P = 0.001, OR = 0.029) while it was not associated with UC in the Han population (P = 0.074, OR = 0.62). Moreover, rs601338 was associated with UC in both Han (P = 0.005, OR = 0.1) and Uyghur populations (P = 0.002, OR = 0.43). Meta analysis showed that rs1047781 and rs601338 conferred risk of UC as compared with the controls [P = 0.005, OR = 0.47; P = 0.0003, OR = 0.35; 95% confidence interval (CI) = 0.31-0.72 and 0.21-0.58], but rs281377 and rs602662 showed no statistically significant differences between patients with UC and controls (P = 0.10, OR = 0.71; P = 0.68, OR = 0.09; 95% CI = 0.47-1.07 and 0.56-1.47).CONCLUSION: Functionally relevant FUT2 gene variants are associated with UC, suggesting that they play a potential role in the pathogenesis of UC and may contribute to the clinical heterogeneity of UC between Han and Uyghur patients. (C) 2012 Baishideng. All rights reserved.