广西黑衣壮儿童哮喘IL-4、IL-13、IL-4R和IL1R1基因多态性研究

发布时间：2018-03-01 18:35

本文关键词： 哮喘易感性基因多态性黑衣壮儿童　出处：《右江民族医学院》2017年硕士论文　论文类型：学位论文

【摘要】：目的研究基因IL-4(rs2227284和rs2243274)、IL-4R(rs1805013和rs3024608)、IL-13(rs20541和rs1295685)、IL1R1(rs1558641和rs949963)位点多态性在黑衣壮儿童人群中的分布频率;初步探讨IL-4(rs2227284和rs2243274)、IL-4R(rs1805013和rs3024608)、IL-13(rs20541和rs1295685)、IL1R1(rs1558641和rs949963)位点多态性与黑衣壮儿童哮喘易感性的关系。方法通过聚合酶链反应-连接酶检测反应(Polymerase Chain Reaction-Ligase Detection Reaction,PCR-LDR)方法对80例哮喘儿童和100例健康儿童的基因IL-4(rs2227284和rs2243274)、IL-4R(rs1805013和rs3024608)、IL-13(rs20541和rs1295685)、IL1R1(rs1558641和rs949963)位点多态性进行基因分型。采用SPSS 17.0统计软件进行数据的统计分析。通过计数法计算哮喘组和健康对照组检测的基因型和等位基因频率,运用Hardy-Weinberg遗传平衡定律检验群体代表性。两组的基因型频率和等位基因频率采用χ2检验作比较。计量资料两组间比较采用t检验。通过使用SHEsis在线工具进行连锁及单倍体分析。以上所有统计分析,P0.05则认为差异有统计学意义。结果(1)IL-4基因rs2227284位点在健康组中基因型分布频率为AA 70.0%、AC26.0%、CC 4.0%,在哮喘组中基因型分布频率AA 72.5%、AC 23.7%、CC 3.8%;在健康组中等位基因分布频率为A 83.0%、C 17.0%,在哮喘组中等位基因分布频率为A 84.4%、C 15.6%。IL-4基因rs2243274位点在健康组中基因型分布频率为AA 62.0%、AG 31.0%、GG 7.0%,在哮喘组中基因型分布频率AA 65.0%、AG 30.0%、GG 5.0%;在健康组中等位基因分布频率为A 77.5%、G 22.5%,在哮喘组中等位基因分布频率为A 80.0%、G 20.0%。(2)IL-4R基因rs3024608位点在健康组中基因型分布频率为CC 76.0%、CG 21.0%、GG 3.0%,在哮喘组中基因型分布频率CC 82.5%、CG 15.0%、GG 2.5%;在健康组中等位基因分布频率为C 86.5%、G 13.5%,在哮喘组中等位基因分布频率为C90.0%、G 10.0%。而IL-4R基因rs1805013位点在黑衣壮人群中未发现多态性,在两组研究对象中只检测到CC基因型。(3)IL-13基因rs20541位点在健康组中基因型分布频率为CC 36.0%、CT 49.0%、TT 15.0%,在哮喘组中基因型分布频率CC 38.8%、CT 48.7%、TT 12.5%;在健康组中等位基因分布频率为C 60.5%、T 39.5%,在哮喘组中等位基因分布频率为C 63.1%、T 36.9%。IL-13基因rs1295685位点在健康组中基因型分布频率为CC 35.0%、CT 51.0%、TT 14.0%,在哮喘组中基因型分布频率CC 37.5%、CT 48.7%、TT 13.8%;在健康组中等位基因分布频率为C 60.5%、T 39.5%,在哮喘组中等位基因分布频率为C 61.9%、T 38.1%。(4)IL1R1基因rs1558641位点在健康组中基因型分布频率为CC 63.0%、CT 34.0%、TT 3.0%,在哮喘组中基因型分布频率CC 50.0%、CT 38.8%、TT 11.2%;在健康组中等位基因分布频率为C 80.0%、T 20.0%,在哮喘组中等位基因分布频率为C 69.4%、T 30.6%。IL1R1基因rs949963位点在健康组中基因型分布频率为GG 63.0%、AG 34.0%、AA 3.0%,在哮喘组中基因型分布频率GG 50.0%、AG 38.8%、AA 11.2%;在健康组中等位基因分布频率为G 80.0%、A 20.0%,在哮喘组中等位基因分布频率为G 69.4%、A 30.6%。(5)IL-4基因rs2227284和rs2243274位点存在强连锁不平衡,IL-13基因rs20541和rs1295685位点存在强连锁不平衡,IL1R1基因rs1558641和rs949963位点存在完全连锁不平衡。(6)IL-4(rs2227284和rs2243274)、IL-4R(rs3024608)、IL-13(rs20541和rs1295685)位点基因型和等位基因频率分布在哮喘组和健康组中比较均无差异,P值均大于0.05。IL1R1基因rs1558641和rs949963位点基因型和等位基因频率在哮喘组和健康组中分布均有统计学差异,P值均小于0.05。rs1558641T/rs949963A单倍型在哮喘组中明显增加与健康组比较,有统计学意义,P值小于0.05。结论在黑衣壮儿童中,IL-4R(rs1805013)位点在黑衣壮儿童中可能不存在多态性;IL-4(rs2227284和rs2243274),IL-4R(rs3024608),IL-13(rs20541和rs1295685),IL1R1(rs1558641和rs949963)位点存在多态性,且基因型频率分布具有民族差异。IL-4(rs2227284和rs2243274),IL-4R(rs3024608),IL-13(rs20541和rs1295685)位点多态性与黑衣壮儿童哮喘易感性可能无关;rs1558641和rs949963位点多态性均与哮喘有关联,单倍型rs1558641T/rs949963A可能是增加哮喘发病的风险因素。
[Abstract]:Objective to study the IL-4 gene (rs2227284 and rs2243274), IL-4R (rs1805013 and rs3024608), IL-13 (rs20541 and rs1295685), IL1R1 (rs1558641 and rs949963) the frequency distribution of polymorphism in Heiyi Zhuang population of children; a preliminary study of the IL-4 (rs2227284 and rs2243274), IL-4R (rs1805013 and rs3024608), IL-13 (rs20541 and rs1295685), IL1R1 (rs1558641 and rs949963) the relationship between polymorphism and Heiyizhuang susceptibility of asthma. Methods by polymerase chain reaction ligase detection reaction (Polymerase Chain Reaction-Ligase Detection Reaction, PCR-LDR) gene IL-4 in 80 cases of children with asthma and 100 healthy children (rs2227284 and rs2243274), IL-4R (rs1805013 and rs3024608) (IL-13, rs20541 and rs1295685), IL1R1 (rs1558641 and rs949963) were genotyped polymorphisms. The data were analyzed by SPSS 17 statistical software. By counting The calculation method of the asthma group and healthy control group to detect the genotype and allele frequency, using the Hardy-Weinberg law of genetic equilibrium inspection group representative. Two groups of genotype and allele frequencies of 2 test was used for comparison. Measurement data between two groups were compared by t test. Analyze the linkage and haploid by using SHEsis online tools. All of the above statistics analysis, P0.05 was considered statistically significant. Results (1) IL-4 rs2227284 gene in the healthy group in genotype distribution frequency of AA 70%, AC26.0%, CC 4%, in the asthma group in genotype frequency distribution of AA 72.5%, AC 23.7%, CC 3.8% allele in the healthy group; the frequency distribution of A 83%, C 17% in asthma group and allele frequency distribution of A 84.4%, C 15.6%.IL-4 rs2243274 gene in the healthy group in genotype distribution frequency of AA 62%, AG 31%, GG 7% in asthma The frequency of AA genotype distribution in group 65%, AG 30%, GG 5% in the healthy group; the allele frequency distribution of A 77.5%, G 22.5% in asthma group and allele frequency distribution of A 80%, G 20.0%. (2) IL-4R rs3024608 gene in the healthy group in genotype distribution frequency of CC 76%, CG 21%, GG 3%, in the asthma group in genotype frequency distribution of CC 82.5%, CG 15%, GG 2.5% in the healthy group; the allele frequency distribution of C 86.5%, G 13.5% in asthma group and allele frequency distribution of C90.0%, G 10.0%. and IL-4R rs1805013 gene in black clothes Zhuang groups found no polymorphism in two, a group of subjects only CC genotype was detected. (3) IL-13 rs20541 gene in the healthy group in genotype distribution frequency of CC 36%, CT 49%, TT 15%, in the asthma group in genotype frequency distribution of CC 38.8%, CT 48.7%, TT 12.5%; allele distribution in the healthy group frequency Rate of C 60.5%, T 39.5% in asthma group and allele frequency distribution of C 63.1%, T 36.9%.IL-13 rs1295685 gene in the healthy group in genotype distribution frequency of CC 35%, CT 51%, TT 14%, in the asthma group in genotype frequency distribution of CC 37.5%, CT 48.7%, TT 13.8% in the healthy group of medium; the allele frequency distribution of C 60.5%, T 39.5% in asthma group and allele frequency distribution of C 61.9%, T 38.1%. (4) IL1R1 rs1558641 gene in the healthy group in genotype distribution frequency of CC 63%, CT 34%, TT 3% in asthma group and genotype distribution frequency of CC 50%, CT 38.8% TT, 11.2%; in the healthy group allele frequency distribution of C 80%, T 20% in asthma group and allele frequency distribution of C 69.4%, T 30.6%.IL1R1 rs949963 gene in the healthy group in genotype distribution frequency of GG 63%, AG 34%, AA 3%, in the asthma group in genotype frequency distribution The rate of GG 50%, AG 38.8%, AA 11.2% in the healthy group; the allele frequency distribution of G 80%, A 20% in asthma group and allele frequency distribution of G 69.4%, A 30.6%. (5) has a strong linkage disequilibrium between IL-4 gene rs2227284 and rs2243274 loci, there is a strong linkage disequilibrium between IL-13 gene rs20541 and rs1295685 site, there is a complete linkage disequilibrium of IL1R1 gene rs1558641 and rs949963 loci. (6) IL-4 (rs2227284 and rs2243274), IL-4R (rs3024608), IL-13 (rs20541 and rs1295685) in asthma group and healthy group showed no significant difference in genotype and allele frequency distribution, P values were greater than rs1558641 and 0.05.IL1R1 gene rs949963 genotype and allele frequencies in the asthma group and the healthy group distribution were statistically significant difference, P values were less than 0.05.rs1558641T/rs949963A haplotypes in asthma group increased significantly compared with the healthy group, there was statistically significant Meaning, P value is less than 0.05. in conclusion Heiyizhuang children, IL-4R (rs1805013) loci may not exist polymorphism in Heiyi Zhuang children; IL-4 (rs2227284 and rs2243274), IL-4R (rs3024608), IL-13 (rs20541 and rs1295685), IL1R1 (rs1558641 and rs949963) in locus polymorphism, and genotype frequency with the distribution of ethnic differences.IL-4 (rs2227284 and rs2243274), IL-4R (rs3024608), IL-13 (rs20541 and rs1295685) may be independent of polymorphism and susceptibility to childhood asthma were Heiyizhuang; rs1558641 and rs949963 polymorphism is associated with asthma, haplotype rs1558641T/rs949963A may increase the incidence of asthma risk factors.

【学位授予单位】：右江民族医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.6

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