UGT1A1基因突变与广西来宾、那坡地区壮汉民族新生儿高胆红素血症的关系研究

发布时间：2018-07-27 09:26

【摘要】：第一部分UGT1A1基因多态性与广西来宾地区壮汉民族新生儿高胆红素血症关系的研究目的：对广西来宾地区部分壮族、汉族以及壮汉混合民族新生儿进行尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因多态性分析,以探讨广西来宾地区壮汉民族新生儿UGT1A1基因多态性与新生儿高胆红素血症关系,并通过不同民族间的横向对比,分析不同民族间UGT1A1基因多态性是否存在差异。方法：对2011年6月至2012年6月广西来宾市人民医院新生儿科收治的147例病因不明的高胆红素血症新生儿(病例组)和73例非高胆红素血症新生儿(对照组)的UGT1A1基因第1及第4外显子进行PCR扩增、凝胶电泳、基因测序。采用卡方检验比较两组间以及不同民族间的等位基因频率差异,对病例组中G71R各基因型的TSB均值比较采用t检验,logistic回归分析TSB342μmol/L的危险因素。结果：两组在第1外显子中只发现G71R基因突变,第4外显子发现任何突变类型。两组G71R等位基因频率分别为0.204和0.034,高胆红素血症新生儿的G71R基因频率高于非高胆红素血症新生儿,差异有统计学意义(P0.001)。高胆红素血症新生儿中壮族、汉族、混合民族的G71R等位基因频率分别为0.19,0.27,0.20,差异无统计学意义。G71R纯合子突变的TSB均值高于杂合子及野生型组,G71R纯合子突变发生TSB342μmol/L的OR为19.000,95%可信区间为(1.989,181.469)。结论：广西来宾地区新生儿UGT1A1基因第1外显子可能只存在G71R基因突变,第4外显子可能不存任何突变类型。G71R基因突变与广西来宾地区新生儿高胆红素血症的发生相关。但是不同民族(壮族、汉族、混合民族)新生儿UGT1A1基因在G71R错义突变基因频率上无明显差别。G71R可能会使高胆红素血症患儿的血清胆红素水平进一步升高,且G71R纯合子发生TSB342μmol/L的危险性是野生型的19倍。第二部分广西黑衣壮族新生儿高胆红素血症与UGT1A1基因多态性的关系研究目的：对广西地区黑衣壮族高胆红素血症新生儿UGT1A1基因多态性进行检测,探讨UGT1A1基因突变是否为广西黑衣壮族新生儿不明原因高胆红素血症发生的因素。方法：对来自广西那坡县人民医院的179例(112例病因不明的高胆红素血症新生儿和67例正常新生儿)黑衣壮族新生儿的UGT1A1基因第1及第4外显子进行PCR扩增、凝胶电泳、基因测序,计算等位基因频率,比较两组间等位基因频率差异。结果：在两组新生儿中只发现G71R基因突变,且等位基因频率分别为0.147和0.052,差异有统计学意义,在两组新生儿UGT1A1基因的第1及第4外显子中均未发现其他突变类型。结论：广西黑衣壮族新生儿UGT1A1基因第1外显子可能只存在G71R基因突变,第4外显子可能不存在任何突变类型。G71R基因突变可能是黑衣壮族新生儿高胆红素血症发生的原因之一。广西地区新生儿高胆红素血症在G71R突变等位基因频率上,壮族、黑衣壮族及汉族间无特异性。
[Abstract]:Part one the relationship between UGT1A1 gene polymorphism and neonatal hyperbilirubinemia in Zhuang nationality, Laibin, Guangxi
Objective: to analyze the polymorphism of uridine two phosphate glucuronidase 1A1 (UGT1A1) gene polymorphism in the newborns of some Zhuang, Han and Zhuang ethnic groups in the Guangxi Laibin area, in order to explore the relationship between the UGT1A1 gene polymorphism and the neonatal Gao Dan erythropoiemia in the Guangxi Laibin region, and through the transversal between different ethnic groups. To compare the differences of UGT1A1 gene polymorphisms among different nationalities.
Methods: 147 neonates with unidentified hyperbilirubinemia (case group) and 73 cases of non high bilirubinemia (control group) were treated with PCR amplification, gel electrophoresis and gene sequencing in 147 neonates with unknown etiology and 73 cases of non hyperbilirubinemia (control group) from June 2011 to June 2012 in Guangxi Laibin People's Hospital. The difference of allele frequency between groups and among different nationalities was used to compare the TSB mean of G71R genotypes in the case group by t test, and the risk factors of TSB342 micron mol/L were analyzed by logistic regression.
Results: only G71R gene mutation was found in first exons, and fourth exons found any type of mutation. The frequency of G71R allele in two groups was 0.204 and 0.034 respectively. The G71R gene frequency of hyperbilirubinemia newborns was higher than that of non hyperbilirubinemia newborns. The difference was statistically significant (P0.001). The G71R allele frequencies of ethnic, Han, and mixed ethnic groups were 0.19,0.27,0.20 respectively, and there was no significant difference in the difference between.G71R homozygote mutation and the heterozygote and the wild type. The OR of the G71R homozygote mutation was TSB342 mol/L OR as the 19.000,95% confidence interval (1.989181.469).
Conclusion: the UGT1A1 gene first exon of newborns in the Guangxi Laibin area may only have G71R gene mutation. Fourth exon may not have any mutation type.G71R gene mutation related to the occurrence of hyperbilirubinemia in the newborns of Guangxi Lai bin area. But the UGT1A1 gene of different ethnic groups (Zhuang, Han, mixed nationality) in the G71R missense There is no obvious difference in the frequency of mutation gene.G71R, which may increase the level of serum bilirubin in children with hyperbilirubinemia, and the risk of G71R homozygote occurrence of TSB342 mu mol/L is 19 times as high as that of the wild type.
The second part is the relationship between UGT1A1 gene polymorphism and neonatal hyperbilirubinemia in Guangxi Zhuang nationality.
Objective: to detect the polymorphism of UGT1A1 gene in neonate with hyperbilirubinemia in Guangxi and to explore whether the mutation of UGT1A1 gene is the factor of unexplained hyperbilirubinemia in Guangxi black clothes Zhuang newborns.
Methods: the UGT1A1 gene first and the 4 exon of 179 cases (112 cases of hyperbilirubinemia and 67 normal newborns) from the people's Hospital of Napo County, Guangxi, were amplified by PCR, gel electrophoresis, gene sequencing, and the frequency of allele frequencies were calculated, and the difference of allele frequencies between the two groups was compared.
Results: only G71R gene mutations were found in the two groups of newborns, and the allele frequencies were 0.147 and 0.052, respectively. The difference was statistically significant. No other mutations were found in the two groups of the two groups of newborns in the first and 4 exons.
Conclusion: the UGT1A1 gene first exon first may only have G71R gene mutation. Fourth exon may not have any mutation type.G71R gene mutation may be one of the causes of hyperbilirubinemia in the black clothes Zhuang newborns. The neonatal Gao Dan erythropoiemia in the Guangxi region is on the G71R mutation allele frequency. There is no specificity between the Zhuang, the black clothes Zhuang and the Han nationality.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R722.17

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