【作者】 陈敏；

【导师】 克力木·阿不都热依木；

【作者基本信息】 新疆医科大学 ， 外科学（专业学位）， 2014， 博士

【摘要】 目的：（1）探讨单中心维吾尔族、汉族胆结石的患病率及可能的风险因素；（2）探讨ApoE基因标签SNP与胆结石之间的关系，维吾尔族、汉族胆结石的可能风险基因型；（3）探讨ApoB基因标签SNP与胆结石之间的关系，维吾尔族、汉族胆结石的可能风险基因型。方法：（1）收集我院体检中心资料齐全者共3288例，统计胆结石总患病率、不同民族患病率、不同性别患病率、不同年龄段患病率；按患病率分层方法统计不同性别、不同年龄段、不同民族胆结石的风险因素行单因素分析，结果有意义者带入非条件多因素Logistic回归，发现胆结石的风险因素，同时探讨胆结石患病风险因素在不同区组间的异同；（2）采用病例-对照研究方法，分别对158名维吾尔胆结石患者及106名维吾尔族对照、110名汉族胆结石患者及106名汉族对照，采用限制性片段长度内切酶方法进行ApoE基因型分型，分析基因型分布的民族间差异、疾病间差异、可能的易感基因型；（3）采用病例-对照研究方法，分别对158名维吾尔胆结石患者及106名维吾尔族对照、110名汉族胆结石患者及106名汉族对照，采用SNaPshot SNP分型技术进行ApoB基因型分型，分析基因型分布的民族间差异、疾病间差异、可能的易感基因型。结果：（1）胆结石患病率存在民族、年龄差异，性别差异：维吾尔族胆结石患病率明显高于汉族（30.66%vs13.39%，P＜0.001）；＞50岁人群胆结石患病率高于≤50岁人群（34.34%vs11.51%，P＜0.001）；女性胆结石患病率明显高于男性（18.14%vs14.61%，P=0.008）。不同年龄段、不同性别间胆结石患病风险因素不同，但结果均提示民族为胆结石的独立风险因素。维吾尔族与汉族胆结石风险因素存在差异。共同因素为：年龄、TG，而汉族胆结石的风险因素还包括：BMI；维吾尔族胆结石患病风险因素还包括：性别、HDL。分析汉族、维吾尔族胆结石患者一般特征发现，维吾尔族胆结石患者相较于汉族患者具有以下特点：患病年龄大、BMI高、LDL高、TC低、女性比例高、脂肪肝比例低。（2）ApoE基因rs405509位点：在维吾尔族人群中，胆结石组与对照组间基因型和等位基因分布有明显差异（P＜0.05）；在汉族人群中，胆结石组与对照组间基因型和等位基因分布有明显的差异（P＜0.05），ApoE基因rs769450位点在维族、汉族人群中，胆结石组与对照组间基因型和等位基因分布均无差异（P＞0.05）；（3）ApoB标签SNPApoB基因rs676210、rs2854725、rs11676704、rs520354和rs1367117位点的基因型和等位基因分布频率在维吾尔族胆结石组和对照组间无差异（P＞0.05）；ApoB基因rs11676704、rs520354位点基因型和等位基因分布频率在汉族胆结石组与对照组间的差异均有统计学意义（P＜0.05）。而rs676210、rs2854725和rs1367117位点基因型和等位基因分布频率在汉族胆结石组和对照组间未见差异（P＞0.05）。结论：（1）胆结石患病率存在年龄、性别、民族差异，维吾尔族胆结石患病率高于汉族，＞50岁人群胆结石患病率显著增高，女性胆结石患病率明显高于男性。民族为胆结石独立风险因素。不同民族间胆结石患病风险因素及胆结石一般特征不尽相同；（2）ApoE基因rs405509位点基因多态性与维吾尔族、汉族胆结石有关联。ApoE基因rs769450位点基因多态性与维吾尔族、汉族胆结石无关联；（3）ApoB rs11676704、rs520354位点基因多态性与汉族胆结石有关联，而与维吾尔族胆结石无关。ApoB基因rs676210、rs2854725、rs1367117位点的基因多态性与维吾尔族、汉族胆结石均无关联。更多还原

【Abstract】 Objective:(1) To explore the prevalence rate of gallstone and the risk factors ofgallstone in Han and Uygur population in One Center;(2) to investigate the relationshipbetween ApoE gene tagging SNPs polymorphism and gallstones;(3) to investigate therelationship between ApoB gene tagging SNPs polymorphism and gallstones. Methods:(1)3288cases in one hospital Health Care Center were used to analyze the prevalencerates of gallstones in different nationalities, moreover, to explore the risk factors ofgallstones in different ethnic populations (Han and Uygur) and in different gender anddifferent ages by the non-conditional Logistic regression; and also to explore the differentrisk factors in different groups;(2) A case-control study including158Uygur gallstonesand106controls as well as110Han gallstones and106controls was designed to observethe relationship between the polymorphisms of ApoE and gallstones by the restrictionfragment length polymorphism;(3) A case-control study including158Uygur gallstonesand106controls as well as110Han gallstones and106controls was designed to observethe relationship between the polymorphisms of ApoB and gallstones by the SNaPshotSNP genotyping. Results:(1) The prevalence rate of gallstone is different in differentethnics、genders and ages. The prevalence rate of gallstone in Uygur populations issignificantly higher than the Han nationality (30.66%vs13.39%, P＜0.05), and so doesin different ages (34.34%vs11.51%, P＜0.05), also does in different genders (18.14%vs14.61%, P＜0.05). The risk factors of gallstone is partly different in different ages andgenders. Interestingly, the ethnic is the common risk factor. So we furtherly compared therisk factors and general data of gallstone in Han and Uygur, we found that TG is the samerisk factors and there are different risk factors and different general characteristics in different ethnics. In Han groups BMI is risk factors and female and fatty Live is riskfactors in Uygur groups. Aged、female、fatty Live、more BMI、lower TC and higher LDLis common in Uygur groups;(2) In the Uyghur population, significant difference ingenotype frequencies and allele frequencies of tagSNPs rs405509were found in theApoE gene between patients with gallstones and controls P＜0.05). In the Han population,the difference between the genotype frequencies and allele frequencies of tagSNPsrs405509between gallstone patients and controls was significant (P＜0.05), but nosignificant difference in genotype frequencies and allele frequencies was found fortagSNPs rs769450(P＞0.05).(3) In the Uyghur population, no significant difference ingenotype or allele frequencies of SNPs rs676210, rs2854725, rs11676704, rs520354, orrs1367117were found in the ApoB gene between patients with gallstones and controls (P＞0.05). In the Han population, the difference between the genotype frequencies andallele frequencies of SNPs rs11676704and rs520354between gallstone patients andcontrols was significant (P＜0.05). No significant difference was found for SNPsrs676210, rs2854725and rs1367117(P＞0.05). Conclusions:(1) The prevalence ofgallstone is higher in Uygur population and aged groups. The risk factors are different indifferent ethnic and ages, also and genders. Ethnic is an important risk factors ingallstone. The general characterics and risk factors are different in different ethnics;(2)The distribution of ApoE rs769450is found difference between Han and Uygurgroups.The distribution of ApoE rs769450is not found difference between Han andUygur groups.(3) ApoB rs11676704and rs520354polymorphisms may be related to riskof developing gallstone in the Han population, but not related to risk of gallstone in theUygur population.ApoB rs676210、rs2854725、rs1367117polymorphisms may be norelation to risk of gallstone in both Uygur and Han population.更多还原