内蒙古西部地区汉族新生儿呼吸窘迫综合征与ABCA3基因的相关性研究

发布时间：2018-03-08 05:25

本文选题：呼吸窘迫综合征　切入点：新生儿　出处：《内蒙古医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:新生儿呼吸窘迫综合征(respiratory distress syndrome of newborn,NRDS)又称新生儿肺透明膜病,发病原因主要是由于肺表面活性物质(pulmonary surfactant,PS)缺乏造成的肺泡张力下降,肺泡扩张受限;临床表现为新生儿生后不久出现进行性加重的呼吸困难、呼吸衰竭等症状。肺表面活性物质中90%的成分为脂类,ATP结合盒转运子A3(ATP—binding cassette transporters A3,ABCA3)作为ABC转运子的亚科,主要协助脂类跨膜转运至板层小体,在板层小体内完成对PS最后的加工和包装过程,对PS的合成和稳态维持起到重要作用。本研究通过对ABCA3外显子10(exon10)进行基因测序和分析,初步探讨ABCA3 exon10区域上是否有基因变异或多态性位点分布,探讨其与内蒙古西部地区汉族NRDS发病的相关性,从基因水平探讨NRDS的发病机制。方法:采用病例对照研究方法,收集于2014年9月-2016年9月在内蒙古医科大学附属医院新生儿重症监护病房(neonatal intensive care unit,NICU)住院的汉族NRDS患儿53例作为病例组,同时间段、同民族、同群体中53例非NRDS汉族新生儿作为对照组。分别提取两组基因组DNA,聚合酶链式反应(polymerase chain reaction,PCR)扩增ABCA3 exon10,并将扩增产物进行直接测序,分析两组ABCA3exon10是否有变异或多态性位点存在。结果:(1)在ABCA3 exon10 rs13332514(F353F)位点存在单个碱基点突变CT,密码子由TTC变为TTT,所编码第353位点氨基酸未发生改变。病例组和对照组均存在该位点点突变,其中NRDS组共有16例,变异率为30.2%,非NRDS组共有7例,变异率为13.2%,NRDS组显著高于非NRDS组(x2=4.498,P=0.034),差异具有统计学意义;(2)NRDS组在ABCA3外显子10 rs13332514(F353F)位点上可检测三种基因型,即CC、CT和TT,其基因型频率分别为:69.8%、20.8%和9.4%,C等位基因频率为80.2%,T等位基因频率为19.8%。对照组可检出2种基因型:即CC和CT,频率分别为86.8%和13.2%,C等位基因频率为93.4%,T等位基因频率为6.6%。NRDS组T等位基因型频率与对照组相比显著增高,差异具有统计学意义(x2=8.065 P0.05)。结论:ABCA3外显子10区域上rs13332514(F353F)位点存在单个碱基点突变CT,该位点变异可能与内蒙古西部地区汉族新生儿发生NRDS有相关性,等位基因T可能是增加该区汉族新生儿发生NRDS的易感因素之一。
[Abstract]:Objective: distress syndrome of newborns with respiratory distress syndrome (distress syndrome of newbornus NRDS) is also known as hyaline membrane disease of the newborn, which is mainly caused by the decrease of alveolar tension and the limitation of alveolar dilatation caused by the deficiency of pulmonary surfactant. The clinical manifestations were progressive dyspnea, respiratory failure and so on. The pulmonary surfactant (90%) was composed of lipoid ATP-binding cassette transporters A3ABCA3 as the subfamily of ABC transporter. It mainly assists lipid transmembrane transport to lamellar bodies, completes the final processing and packaging of PS in the lamellar bodies, and plays an important role in the synthesis and homeostasis of PS. In this study, exon 10exon 10 of ABCA3 was sequenced and analyzed. To explore the distribution of gene variation or polymorphism loci in ABCA3 exon10 region, to explore the correlation between NRDS and NRDS in Han nationality in western Inner Mongolia, and to explore the pathogenesis of NRDS at gene level. Methods: a case-control study was conducted. From September 2014 to September 2016, 53 NRDS children of Han nationality who were hospitalized in the Neonatal intensive care Unit of the affiliated Hospital of Inner Mongolia Medical University were selected as the case group, at the same time and in the same nationality. In the same population, 53 non NRDS Han newborns were used as control group. Two groups of genomic DNAs were extracted, polymerase chain reactionated PCR was used to amplify ABCA3 exon 10, and the amplified products were sequenced directly. The results showed that there was a single base mutation at the ABCA3exon10 rs13332514F353F site, the codon changed from TTC to TTT.The amino acid at the 353rd site was not changed. Both the case group and the control group did not change. There is a point mutation at the site, There were 16 cases in NRDS group and 7 cases in non-#en1# group. The variation rate was significantly higher in NRDS group than in non-#en2# group. The difference was statistically significant in ABCA3 exon 10rs13332514F353F. The genotype frequencies of CCT CT and TTT were 20. 8% and 9. 4%, respectively. The allele frequency of C was 80. 2% and T allele frequency was 19. 8%. In the control group, two genotypes were detected: CC and CT. the frequencies were 86.8% and 13. 2%, respectively. The frequency of T allele was 93. 4T allele. The frequency of T alleles in the 6.6B. NRDS group was significantly higher than that in the control group. Conclusion there is a single base point mutation at rs13332514F353F in exon 10 of ABCA3, which may be related to the occurrence of NRDS in neonates of Han nationality in western Inner Mongolia. Allele T may be one of the risk factors to increase the incidence of NRDS in neonates of Han nationality in this area.
【学位授予单位】：内蒙古医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R722.1

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