摘要
目的：探讨维生素D受体（VDR）基因多态性及血清25-羟维生素D[25（OH）D]水平与溃疡性结肠炎（ UC）的关系。方法2004年7月至2013年7月从温州市4家医院收集404例UC患者作为UC组，同期在温州医科大学附属第二医院体检中心收集612名健康体检者作为对照组，采用微测序技术检测VDR（ FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ）4种单核苷酸多态性。在UC组和对照组之间，采用χ2检验及Bonferroni 校正分析等位基因和基因型频率差异。利用随机数字表法从中选取75例UC患者和120名对照者，采用电化学发光法检测血清25（ OH） D水平，经t检验比较组间差异。结果经Bonferroni校正后，与对照组比较，UC组中VDR（ Fok Ⅰ、Bsm Ⅰ、Apa Ⅰ、Taq Ⅰ）4个位点的突变等位基因和基因型频率差异均无统计学意义（均P＞0.0125）。依据“Truelove ＆ Witts严重程度分型标准”分组，轻中度UC患者中FokⅠ的突变等位基因（ C）和基因型（ TC＋CC）频率均显著高于重度患者[54.37％（373／686）比37.70％（46／122），81.92％（281／343）比55.74％（34／61），均P＜0.01]。单倍型分析发现VDR（ Bsm Ⅰ、Apa Ⅰ、TaqⅠ）3个位点紧密连锁，UC组中AAC单倍型的频率显著低于对照组[3.58％（29／808）比6.01％（74／1224），P＝0.012]。 UC组中血清25（OH）D平均水平显著低于对照组[（48±17）比（54±18）nmol／L，P＝0.017]；并且轻中度UC患者显著高于重度患者，广泛结肠炎患者显著低于远端结肠炎患者（均P＜0.01）。线性回归分析显示UC患者中血清25（OH）D水平与血红蛋白呈独立正相关（β＝0.499，P＜0.01），与C反应蛋白及白细胞计数呈独立负相关（β＝-0.346，P＜0.01；β＝-0.291，P＝0.002）。经Logistic回归分析发现Bsm Ⅰ突变基因型（GA／AA）是UC的独立保护因素（OR＝0.328，P＝0.028），Fok Ⅰ突变基因型（TC／CC）与血清25（OH）D缺乏（＜50.0
Objective To explore the associations of ulcerative colitis （ UC ） with vitamin D receptor （VDR） gene polymorphisms and serum levels of 25-hydroxyl vitamin D [25（OH） D].Methods From July 2004 to July 2013, a total of 404 UC patients were recruited from 4 hospitals of Wenzhou City.A total of 612 controls were collected from Health Examination Center of Second Affiliated Hospital of Wenzhou Medical University.Four single nucleotide polymorphisms of VDR （ Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ, Taq Ⅰ） were detected by mini-sequencing technique.The frequencies of minor allele and genotype of VDR were compared between UC patients and the controls by χ2 test and Bonferroni correction.Moreover, 75 UC＆amp;nbsp;patients and 120 gender-and age-matched healthy controls during the corresponding period were randomly selected for determining the serum levels of 25（OH）D by electrochemiluminescence immunoassay and were compared by Student′s test.Results After Bonferroni correction , mutant allele and genotype frequencies of VDR （ Fok Ⅰ, Bsm Ⅰ, ApaⅠ, TaqⅠ） did not statistically differ between UC patients and the controls （all P〉0.012 5）.Stratification by the Truelove ＆amp; Witts severity index , mutant allele （C） and genotype （ TC＋CC） of VDR（ Fok Ⅰ） were significantly higher in patients with mild and moderate UC than in those with severe UC （ 54.37%（ 373/686 ） vs 37.70%（ 46/122 ） , 81.92%（ 281/343 ） vs 55.74%（ 34/61 ） , both P〈0.01）.Haplotype analysis showed that three polymorphic loci of Bsm Ⅰ, Apa Ⅰand Taq Ⅰwere in a complete linkage disequilibrium.The AAC haplotype decreased significantly in UC patients compared to the controls （3.58%（29/808） vs 6.01%（74/1 224）, P=0.012）.The average serum levels of 25（OH） D in UC patients were significantly lower than those in the controls （（48 ±17） vs （54 ±18）nmol/L, P=0.017）.Furthermore, the average serum levels of 25（OH）D were significantly higher in patients with mild and moderat
出处
《中华医学杂志》
CAS
CSCD
北大核心
2014年第14期1060-1066,共7页
National Medical Journal of China
基金
浙江省卫生厅资助（2012KYA132）
温州市科技局资助（Y20110027）
关键词
结肠炎
溃疡性
维生素D
多态性
单核苷酸
Colitis,Ulcerative
Vitamin D
Polymorphism,single nucleotide
