【作者】 李大伟；

【导师】 刘海南；

【作者基本信息】 山东大学 ， 外科学， 2010， 硕士

【摘要】 目的1.探讨硫酸乙酰肝素蛋白多糖(HSPG)基因rs3767140位点多态性与中国汉族人群草酸钙肾结石易感性的关系。2.分析硫酸乙酰肝素蛋白多糖(HSPG)基因rs3767140位点多态性与中国汉族人群草酸钙肾结石复发的相关性。方法以病例对照研究方法,提取143例草酸钙肾结石患者及157例健康对照者外周血标本基因组DNA,应用聚合酶链反应一限制性片断长度多态性(PCR-RFLP)分析技术,检测并分析HSPG基因rs3767140位点单核甘酸多态性与草酸钙肾结石形成及复发的关系。记录并比较两组间年龄、性别构成比、体重、身高和身体质量指数之间的差异。统计学处理使用SPSS13.0软件完成,组间计量资料以均数±标准差((?)±s)表示,计量资料比较使用t检验,计数资料比较采用χ2检验,使用非条件Logistic回归进行多因素分析计算各基因型与草酸钙尿路结石复发的关联强度。结果健康对照组与结石组临床资料比较：两组间年龄、性别构成比、体重、身高和身体质量指数之间的差异无统计学意义(P>0.05)；HSPG基因等位基因频率分布符合Hardy-Weinberg平衡定律(结石组χ2=0.094,P>0.05；对照组χ2=0.107,P>0.05),具有群体代表性；结石组GG+GT、TT基因型分布频率分别为69.23％、30.77％,健康对照组分别为79.62％、20.38％,差异有统计学意义(P<0.05),TT基因型个体患结石的风险是其它基因型的1.736倍(OR=1.736,95％CI=1.026～2.938),结石组与对照组等位基因G、T分布频率分别为：45.10％、55.90％和54.14％、45.86％(P<0.05)；未发现HSPG基因多态性与草酸钙结石的复发相关。结论1.山东汉族健康人群中存在HSPG基因rs3767140位点单核苷酸多态性。G等位基因在健康人群中的分布频率大约为54.14％。2.HSPG基因rs3767140位点多态性与草酸钙肾结石发生有相关关系。TT基因型可作为草酸钙结石危险因素的标志。TT基因型个体患结石的风险是其它基因型的1.736倍。3.等位基因G可能是结石形成的保护因素。4.HSPG基因rs3767140位点多态性可能与草酸钙尿路结石复发无相关关系。更多还原

【Abstract】 Objective:1.To explore the potential association between the Heparan Sulfate Proteoglycan gene polymorphism and genetic susceptibility to calcium oxalate nephrolithiasis in Chinese Han population.2.To investigate correlation of the Heparan Sulfate Proteoglycan gene polymorphism with calcium oxalate stone recurrence.Methods:In this study,totally 143 patients diagnosed with calcium oxalate urolithiasis were studied.In addition,157 age-matched healthy controls were enrolled.Genomic DNA were extracted from blood samples.Based on case-control study,Heparan Sulfate Proteogylcan gene polymorphism (rs3767140) was determined by polymerase chain reaction and restriction fraction length polymorphism(PCR-RFLP) with BamH I digestion.The correlation of the heparan sulfate proteoglycan gene polymorphism with calcium oxalate stone and calcium oxalate stone recurrence was investigated.Meanwhile age,sex composition,weight,height and body mass index (BMI) were analyzed.All statistical tests were carried out by the SPSS 13.0 software.The associations of clinical features,including age,weight,hight and body mass index (BMI), were tested using T test.Measurement date interclass was indicated with x±s.The differences in sex composition and genotype frequencies between the cases and controls were tested using x2-test. Unconditional logistic regression model was used to assess the association between correlative factors and calcium oxalate stone recurrence.Results:Differences of age,sex composition,weight,height and body mass index (BMI) between the two groups were not significant(P>0.05).The distribution frequencies of site rs3767140 genotype and alleles in the two groups followed the Hardy-Weinberg equilibrium(P> 0.05).The distribution frequencies of the GG+GT,TT genotypes were 69.23%,30.77% in oxalate calcium urolithiasis group and 79.62%,20.38% respectively in healthy control group.The differences between the two groups were statistically significant(P<0.05).The distribution frequencies of G and T alleles in stone and control groups were 45.10%,55.90% and 54.14%,45.86% respectively,and statistical differences were observed(P<0.05).The subjects with TT genotype yielded a 1.736 fold increased risk for calcium oxalate nephrolithiasis,compared with subjects with GT+GG genotype(OR=1.736,95%CI=1.026～2.938),however,we did not find the association between HSPG gene polymorphism and the possibility of stone recurrence.Conclusions:1.There are G/T polymorphisms in HSPG gene in Chinese Han population of Shandong Province.The allele G frequency in healthy control is about 54.14%.2.There is significant association between HSPG gene polymorphism and calcium oxalate nephrolithiasis. The TT genotype may be a good genetic marker for calcium oxalate nephrolithiasis.The subjects with TT genotype yielded a 1.736 fold increased risk for calcium oxalate nephrolithiasis,compared with subjects with GT+GG genotypes.3.Allele G may be a protective factor for calcium oxalate nephrolithiasis..4.There is no significant association between HSPG gene polymorphism and calcium oxalate stone recurrence.更多还原