ADAM33基因DNA甲基化水平与哮喘患者的关联性研究
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摘要
目的探讨ADAM33基因DNA甲基化水平与新疆成人哮喘的关联性。方法选择2013年11月-2014年12月经新疆医科大学第一附属医院呼吸科住院的、明确诊断哮喘的成人患者10例作为哮喘组,对照组10例选取了同期、同居住地、性别搭配、年龄相距在5岁以内且与哮喘组无血缘关系的健康体检者,采用病例-对照的研究方法,运用亚硫酸氢盐PCR测序技术进行甲基化程度检测,对DNA序列和测序序列进行比对分析。结果哮喘组CpGⅠ甲基化程度为(63.88±9.86),对照组CpGⅠ甲基化程度为(53.67±5.44),差异有统计学意义(P=0.010)。在哮喘组和对照组之间比较,ADAM33基因CpG岛Ⅰ中存在19个CpG位点差异有统计学意义(P<0.05)。CpG岛ⅠDNA甲基化程度与FEV1/FVC呈负相关,差异具有统计学意义(γ=-0.515,P=0.020),CpG岛ⅠDNA甲基化程度与FEV1/预计值呈负相关,差异无统计学意义(γ=-0.181,P=0.446)。结论 ADAM33基因CpG岛Ⅰ存在部分CpG位点与哮喘有相关性,CpG岛Ⅰ的甲基化程度与哮喘有相关性,CpG岛I DNA甲基化程度与肺功能存在一定相关性。
Objective Selected ne CpG island of the ADAM33 gene to detect the correlation between the DNA methylation levels of ADAM33 gene and asthma in Chinese adults. Methods Ten adult patients with asthma who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Xinjiang Medical University from November 2013 to December 2014 were selected as asthma group. Ten healthy people who had no blood relationship with asthma group were selected as control group. By using the case-control study method, the genomic DNA of the samples was extracted by the method of sequencing of bisulfite. The levels of DNA sequences and sequencing sequences were analyzed by BiQ Analyzer analysis software. Results The methylation degree of CpG I in the asthma and control group were(63.88±9.86) and(53.67±5.44) respectively. The difference was statistically significant(P=0.010). There were 19 CpG loci differences in CpG island I of ADAM33 gene between the asthma group and control group with statistical significance(P<0.05). The methylation degree of CpG island I DNA was negatively correlated with FEV1/FVC, with significant difference(γ=-0.515, P=0.020). The methylation degree of CpG island I DNA was negatively correlated with FEV1/predicted value, with no significant difference(γ=-0.181, P=0.446). Conclusion Some CpG loci in CpG island I of ADAM33 gene are correlated with asthma, the degree of methylation of CpG island I is correlated with asthma, and the degree of DNA methylation of CpG island I is correlated with pulmonary function.
Objective Selected ne CpG island of the ADAM33 gene to detect the correlation between the DNA methylation levels of ADAM33 gene and asthma in Chinese adults. Methods Ten adult patients with asthma who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Xinjiang Medical University from November 2013 to December 2014 were selected as asthma group. Ten healthy people who had no blood relationship with asthma group were selected as control group. By using the case-control study method, the genomic DNA of the samples was extracted by the method of sequencing of bisulfite. The levels of DNA sequences and sequencing sequences were analyzed by BiQ Analyzer analysis software. Results The methylation degree of CpG I in the asthma and control group were(63.88±9.86) and(53.67±5.44) respectively. The difference was statistically significant(P=0.010). There were 19 CpG loci differences in CpG island I of ADAM33 gene between the asthma group and control group with statistical significance(P<0.05). The methylation degree of CpG island I DNA was negatively correlated with FEV1/FVC, with significant difference(γ=-0.515, P=0.020). The methylation degree of CpG island I DNA was negatively correlated with FEV1/predicted value, with no significant difference(γ=-0.181, P=0.446). Conclusion Some CpG loci in CpG island I of ADAM33 gene are correlated with asthma, the degree of methylation of CpG island I is correlated with asthma, and the degree of DNA methylation of CpG island I is correlated with pulmonary function.
引文
[1] National Heart,Lung and Blood Insitiute (NHLBI)/World Health Organization(WHO).Global strategry for asthma magement and prevention.Global Initiative for asthma[M].United States:NIH Pullication,2011:1-124.
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[3] YANG P J,LI R N,HUANG C C,et al.The Methylation patterns of a disintegrin and metalloproteinase 33gene(ADAM33)in adult asthma[J].Int Arch Allergy Immunol,2013,161:74-80.
[4] DEL MASTRO R G,TURENNE L,GIESE H,et al.Mechanistic role of a disease-associated genetic variant within the ADAM33 asthma susceptibility gene[J].BMC Med Genet,2007,8(8):46.
[5] 李红梅,何庆南.免疫调节剂在哮喘治疗中的研究进展[J].国际儿科学杂志,2010,37(2):196-199.
[6] 韩继红,肖丽,都雯,等.新疆地区支气管哮喘患者IL-4基因甲基化的研究[J].新疆医科大学学报,2017,40(9):1191-1194.
[2] NAUMOVA A K,AL TUWAIJRI A,MORIN A,et al.Sex-and age-dependent DNA methylation at the 17q12-q21 locus associated with childhood asthma[J].Hum Genet,2013,132:811-822.
[3] YANG P J,LI R N,HUANG C C,et al.The Methylation patterns of a disintegrin and metalloproteinase 33gene(ADAM33)in adult asthma[J].Int Arch Allergy Immunol,2013,161:74-80.
[4] DEL MASTRO R G,TURENNE L,GIESE H,et al.Mechanistic role of a disease-associated genetic variant within the ADAM33 asthma susceptibility gene[J].BMC Med Genet,2007,8(8):46.
[5] 李红梅,何庆南.免疫调节剂在哮喘治疗中的研究进展[J].国际儿科学杂志,2010,37(2):196-199.
[6] 韩继红,肖丽,都雯,等.新疆地区支气管哮喘患者IL-4基因甲基化的研究[J].新疆医科大学学报,2017,40(9):1191-1194.