巨噬细胞炎性蛋白1 α和载脂蛋白E基因多态性与炎症性肠病易感性的关系

Association of combined polymorphisms in MIP-lα and ApoE genes with the susceptibility of inflammatory bowel disease

目的探讨巨噬细胞炎性蛋白lα（MIP-lα）基因和载脂蛋白E（ApoE）基因多态性是否与炎症性肠病（IBD）的发生相关，并探讨这两个基因之间的相互作用。方法采用聚合酶链反应．限制性片段长度多态性方法，在183例IBD患者[包括142例溃疡性结肠炎（UC）患者和41例克罗恩病（CD）患者]以及160名健康对照者中检测MIP-lα和ApoE等位基因和基因型的频率。结果携带MIP-lα-906（TA）6／（TA）。基因型或者APOE4ε4等位基因可以增加UC的发病风险，UC患者组MIP-lα-906位点（TA）6／（TA）6基因型频率为50％，显著高于正常对照组中的34％（OR=1．909，95％CI=1．204—3．028）；UC患者ApoEs,4＋基因型频率为40．8％，显著高于正常对照组中的22．5％（OR：2．379，95％CI=1．451～3．896）。同时携带MIP-lα-906（TA）6／（TA）6和APOE484的个体发生UC的风险更大（P〈0．01，OR=3．288，95％CI=1．777-6．084）。而CD组与对照组间的MIP-lα和ApoE基因多态频率差异无统计学意义。结论MIP-1α基因-906（TA）6／（TA）。多态性和APOE4ε4基因多态性可能是UC发病的遗传危险因素；MIP-1α基因多态性与ApoE基因多态性之间有协同作用，ApoE4ε4等位基因与MIP-lαt-906（TA）6／（TA）。基因型同时存在时，患UC的危险性显著提高．

Objective To investigate whether the macrophage inflammatory protein 1 alpha （MIP- lα） and apolipoprotein E （ApoE） gene potymorphisms, either alone or in combination, affect the susceptibility to inflammatory bowel disease （IBD）. Methods Genomic DNA of IBD patients with Crohn＇s disease （CD, n=41） and with ulcerative colitis （UC, n = 142） and healthy controls （n = 160） was extracted and genotyped for the MIP-lα and ApoE gene polymorphisms by restriction fragment length polymorphism assay. Results MIP-lα -906 （TA）6/（TA）6homozygotes had a significantly elevated risk of UC （ OR = 1. 909, 95% CI = 1. 204 - 3.028 ）. The carriers of APOE4ε4 were at a significantly higher risk for UC with OR of 2. 379 （95% CI= 1. 451 -3. 896）. And a combination of these two loci, MIP-lα -906 （TA） 6/（TA） 6/APOE4ε4 were strongly associated with a higher risk of UC （ OR = 3. 288 ; 95% CI = 1. 777 - 6. 084）. Conclusion The polymorphisms of MIP-lα -906 （TA）6/（ TA ）6 and ApoE are probably independent genetic risk factors for UC. And the coexistence of both may exert an additive effect on the UC risks.