睾素2(SPOCK2)基因多态性与昆明地区新生儿支气管肺发育不良相关性
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摘要
目的探讨睾素2(SPOCK2)基因多态性与昆明地区新生儿支气管肺发育不良(BPD)的相关性。方法选取2017年1-12月在云南省第一人民医院新生儿科住院的早产儿。56例患有BPD的早产儿为BPD组(其中男30例,女26例)。选取同期入住云南省第一人民医院NICU无肺部疾病的早产儿76例作为对照组(其中男30例,女46例)。采用聚合酶链式反应(PCR)对SPOCK2基因多态性位点rs1245560和rs1049269进行检测。结果两组SPOCK2基因型频率均符合Hardy-Weinberg平衡,具有种群代表性。两组均以rs1245560 AC基因型和rs1049269 AG基因型的分布频率最高,但在两组人群中的分布差异均无统计学意义(P=0.249和P=0.060)。基因型分析显示,rs1245560的AA、CC和AC基因型在对照组和BPD组中的分布差异无统计学意义(分别为21.4%vs. 28.9%;17.9%vs. 21.1%;50.0%vs. 60.7%,P>0.05)。rs1049269的AA和GG基因型在两组中分布差异无统计学意义(分别为25.0%vs. 44.7%;32.1%vs.23.7%,均P>0.05);AG基因型在BPD组的分布频率明显高于对照组(42.9%vs.31.6%,P=0.039)。等位基因分析显示,rs1245560 A和C等位基因频率分布差异无统计学意义(48.2%vs. 46.1%,P=0.803);rs1049269 G等位基因频率在BPD组中明显高于对照组(53.6%vs. 39.5%,P=0.025)。结论 SPOCK2基因多态性位点rs1049269AG基因型和G等位基因频率和BPD有关,是BPD发病的高危易感因素。
Objective To investigate the relationship between single nucleotide polymorphism(SNP)ofSPOCK2 and bronchopulmonary dysplasia(BPD).MethodsA total of 76 BPD group and 56 patients withoutlung disease in control group from 2017.1 to 2017.12 were included in this study. PCR-DNA sequence was appliedto detect the genotypes of 2 SNPs(rs1245560 and rs1049269).Resultsrs1245560:AA,CC and AC genotypefrequencies in BPD and control group were 21.4%,17.9% and 60.7% vs. 28.9%,21.1% and 50.0%,respectively.Compared with control group,the genotype and allele frequencies were similar in BPD group(P > 0.05).rs1245560:AA,GG and AG genotype frequencies in BPD and control group were 25.0%,32.1% and 42.9% vs.44.7%,23.7% and 31.6%,respectively. Compared with control group,the genotype AG frequencies were higherin BPD group(P=0.039). There was no significant difference in the allele C frequencies of rs1245560 betweenboth groups(P=0.803);the allele G frequencies of rs1049269 was higher in BPD group with statistical difference(P=0.025).ConclusionsSPOCK2 gene polymorphism rs1049269 in Kunming pediatric population is a suscepti-bility factor for BPD,the AG genotype and G allele increase the risk of getting BPD.
Objective To investigate the relationship between single nucleotide polymorphism(SNP)ofSPOCK2 and bronchopulmonary dysplasia(BPD).MethodsA total of 76 BPD group and 56 patients withoutlung disease in control group from 2017.1 to 2017.12 were included in this study. PCR-DNA sequence was appliedto detect the genotypes of 2 SNPs(rs1245560 and rs1049269).Resultsrs1245560:AA,CC and AC genotypefrequencies in BPD and control group were 21.4%,17.9% and 60.7% vs. 28.9%,21.1% and 50.0%,respectively.Compared with control group,the genotype and allele frequencies were similar in BPD group(P > 0.05).rs1245560:AA,GG and AG genotype frequencies in BPD and control group were 25.0%,32.1% and 42.9% vs.44.7%,23.7% and 31.6%,respectively. Compared with control group,the genotype AG frequencies were higherin BPD group(P=0.039). There was no significant difference in the allele C frequencies of rs1245560 betweenboth groups(P=0.803);the allele G frequencies of rs1049269 was higher in BPD group with statistical difference(P=0.025).ConclusionsSPOCK2 gene polymorphism rs1049269 in Kunming pediatric population is a suscepti-bility factor for BPD,the AG genotype and G allele increase the risk of getting BPD.
引文
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[14]CHEN H,ZHENG W.Association of cytokine gene polymorphisms with bronchopulmonary dysplasia in Han Chinese newborns[J].Pediatr Pulmonol,2018,53(1):50-56.
[15]WONG M,REYES J,LAPIDUS-KROL E,et al.Pulmonary hypertension in congenital diaphragmatic hernia patients:Prognostic markers and long-term outcomes[J].J Pediatr Surg,2018,53(5):918-924.
[16]KICINSKI P,KESIAK M,NOWICZEWSKI M,et al.Bronchopulmonary dysplasia in very and extremely low birth weight infantsanalysis of selected risk factors[J].Pol Merkur Lekarski,2017,42(248):71-75.
[17]张林,杨晓燕,石晶.极低出生体重儿支气管肺发育不良影响因素分析[J].中华妇幼临床医学杂志(电子版),2017,(5):518-523.
[18]黄丽萍,肖玲莉,刘江勤.超低出生体重儿43例临床分析[J].中国新生儿科杂志,2014,29(3):145-148.
[19]BHANDARI A,PANITCH H B.Pulmonary outcomes in bronchopulmonary dysplasia[C].Semin Perinatol,2006,30(4):219-226.
[20]袁文浩,常立文,李文斌,等.血管内皮生长因子基因多态性与支气管肺发育不良相关性研究[J].中国实用儿科杂志,2012,27(9):682-685.
[21]卢维城,郑旭,林静,等.肺表面活性物质蛋白B基因多态性与早产儿支气管肺发育不良的相关性[J].中华实用儿科临床杂志,2013,28(2):118-121.
[22]周玉容,常立文,李文斌,等.武汉汉族新生儿中肺表面活性物质蛋白D基因多态性及其与支气管肺发育不良相关性分析[J].中国病理生理杂志,2011,27(5):968-971.
[23]赵玲霞,李文斌,蔡保欢,等.支气管肺发育不良患儿肺表面活性蛋白-B内含子4基因多态性[J].中华围产医学杂志,2012,15(5):267-272.
[24]齐倩,胡晓琳.谷胱甘肽S-转移酶P1基因多态性与支气管肺发育不良的关系研究[J].中国全科医学,2016,19(34):4213-4215.
[25]陈涛,胡毓华,陆超.高氧肺损伤新生大鼠肺组织中SPOCK2基因表达的研究[J].南京医科大学学报:自然科学版,2018,38(3):299-304.
[26]HADCHOUEL A,FRANCO-MONTOYA M L,DELACOURTC.Altered lung development in bronchopulmonary dysplasia[J].Birth Defects Res A Clin Mol Teratol,2014,100(3):158-167.
[27]WANG H,JULIEN K R S,STEVENSON D K,et al.A genomewide association study(GWAS)for bronchopulmonary dysplasia[J].Pediatrics,2013,132(2):290-297.
[2]章礼真.支气管肺发育不良发病机制及防治策略研究进展[J].安徽医学,2017,38(3):385-388.
[3]ALTIT G,DANCEA A,RENAUD C,et al.Pathophysiology,screening and diagnosis of pulmonary hypertension in infants with bronchopulmonary dysplasia-a review of the literature[J].Paediatr Respir Rev,2017,23:16-26.
[4]MCEVOY C T,DURAND M.Anti-VEGF Antagonists,a potential primary prevention for bronchopulmonary dysplasia?[J].Am J Respir Crit Care Med,2018,197(6):703-704..
[5]LAL C V,AMBALAVANAN N.Cellular and humoral biomarkers of Bronchopulmonary Dysplasia[J].Early Hum Dev,2017,105:35-39.
[6]YU K H,LI J,SNYDER M,et al.The genetic predisposition to bronchopulmonary dysplasia[J].Curr Opin Pediatr,2016,28(3):318-323.
[7]LAL C V,AMBALAVANAN N.Genetic predisposition to bronchopulmonary dysplasia[C].Semin Perinatol,2015,39(8):584-591.
[8]AMBALAVANAN N,COTTEN C M,PAGE G P,et al.Integrated genomic analyses in bronchopulmonary dysplasia[J].J Pediatr,2015,166(3):531-537.
[9]MAHLMAN M,KARJALAINEN M K,HUUSKO J M,et al.Genome-wide association study of bronchopulmonary dysplasia:a potential role for variants near the CRP gene[J].Scientific reports,2017,7(1):9271.
[10]HADCHOUEL A,DURRMEYER X,BOUZIGON E,et al.Identification of SPOCK2 as a susceptibility gene for bronchopulmonary dysplasia[J].Am J Respir Crit Care Med,2011,184(10):1164-1170.
[11]NAGIUB M,KANAAN U,SIMON D,et al.Risk factors for development of pulmonary hypertension in infants with bronchopulmonary dysplasia:systematic review and meta-analysis[J].Paediatr Respir Rev,2017,23:27-32.
[12]CHEN Y,YE Z Z,LU G J.Risk factors of bronchopulmonary dysplasia in very low birth weight infants[J].J Applied Clini Pediatr,2007,22(2):109.
[13]BALENA-BORNEMAN J,AMBALAVANAN N,TIWARI H K,et al.Biomarkers associated with bronchopulmonary dysplasia/mortality in premature infants[J].Pediatr Res,2017,81(3):519-525.
[14]CHEN H,ZHENG W.Association of cytokine gene polymorphisms with bronchopulmonary dysplasia in Han Chinese newborns[J].Pediatr Pulmonol,2018,53(1):50-56.
[15]WONG M,REYES J,LAPIDUS-KROL E,et al.Pulmonary hypertension in congenital diaphragmatic hernia patients:Prognostic markers and long-term outcomes[J].J Pediatr Surg,2018,53(5):918-924.
[16]KICINSKI P,KESIAK M,NOWICZEWSKI M,et al.Bronchopulmonary dysplasia in very and extremely low birth weight infantsanalysis of selected risk factors[J].Pol Merkur Lekarski,2017,42(248):71-75.
[17]张林,杨晓燕,石晶.极低出生体重儿支气管肺发育不良影响因素分析[J].中华妇幼临床医学杂志(电子版),2017,(5):518-523.
[18]黄丽萍,肖玲莉,刘江勤.超低出生体重儿43例临床分析[J].中国新生儿科杂志,2014,29(3):145-148.
[19]BHANDARI A,PANITCH H B.Pulmonary outcomes in bronchopulmonary dysplasia[C].Semin Perinatol,2006,30(4):219-226.
[20]袁文浩,常立文,李文斌,等.血管内皮生长因子基因多态性与支气管肺发育不良相关性研究[J].中国实用儿科杂志,2012,27(9):682-685.
[21]卢维城,郑旭,林静,等.肺表面活性物质蛋白B基因多态性与早产儿支气管肺发育不良的相关性[J].中华实用儿科临床杂志,2013,28(2):118-121.
[22]周玉容,常立文,李文斌,等.武汉汉族新生儿中肺表面活性物质蛋白D基因多态性及其与支气管肺发育不良相关性分析[J].中国病理生理杂志,2011,27(5):968-971.
[23]赵玲霞,李文斌,蔡保欢,等.支气管肺发育不良患儿肺表面活性蛋白-B内含子4基因多态性[J].中华围产医学杂志,2012,15(5):267-272.
[24]齐倩,胡晓琳.谷胱甘肽S-转移酶P1基因多态性与支气管肺发育不良的关系研究[J].中国全科医学,2016,19(34):4213-4215.
[25]陈涛,胡毓华,陆超.高氧肺损伤新生大鼠肺组织中SPOCK2基因表达的研究[J].南京医科大学学报:自然科学版,2018,38(3):299-304.
[26]HADCHOUEL A,FRANCO-MONTOYA M L,DELACOURTC.Altered lung development in bronchopulmonary dysplasia[J].Birth Defects Res A Clin Mol Teratol,2014,100(3):158-167.
[27]WANG H,JULIEN K R S,STEVENSON D K,et al.A genomewide association study(GWAS)for bronchopulmonary dysplasia[J].Pediatrics,2013,132(2):290-297.