汉族早产儿支气管肺发育不良易感基因筛查

Screening of susceptibility genes for bronchopulmonary dysplasia in Han premature infants

目的 探讨汉族早产儿支气管肺发育不良（BPD）易感基因位点多态性与BPD 发生发展的关系。方法 根据国内外文献，筛选出28个可能与 BPD 发生发展有关的候选基因位点；收集2013年4月至12月在广东省人民医院住院的胎龄≤32周、出生体质量≤1 500 g的46例汉族早产儿。其中 BPD 患儿31例（BPD组），非BPD患儿15例（对照组）。2组早产儿均于入院3 d内采血，提取DNA后应用PCR扩增、单碱基延伸及DNA质谱法对28个基因位点进行检测，并分析基因位点与 BPD 发生的关系。结果 28个基因位点中，14个基因型分布符合Hardy-W einberg平衡定律（P 〉0.05），具有群体代表性，列入候选基因。BPD 组患儿肿瘤坏死因子α（TNF-α）基因位点rs1799724和 Toll样受体-10（TLR-10）基因位点 rs11096955基因型发生变异，TNF-α基因位点 rs1799724 CC明显增多［93.5%（29/31例）］、TT明显减少［0（0/31例）］，与对照组［33.3%（5/15例）、20.0%（3/15例）］比较差异有统计学意义（χ^2=18.044，P 〈0.01）；TLR-10基因位点 rs11096955 AC明显增多［64.5%（20/31例）］、CC明显减少［12.9%（4/31例）］，与对照组［33.3%（5/15例）、46.7%（7/15例）］比较差异有统计学意义（χ^2=6.252，P =0.043）；BPD 组 TNF-α 基因位点 rs1799724中 C等位基因分布频率［93.5%（29/31例）］明显增高，与对照组［46.7%（7/15例）］比较差异有统计学意义（χ^2=23.833，P 〈0.01）。未发现与BPD严重程度有关的基因位点（P 〉0.05）。结论 TNF-α、TLR-10基因位点多态性可能与汉族早产儿BPD发生有关；TNF-α基因位点rs1799724 CC基因型和TLR-10基因位点rs11096955 AC基因型可能是 BPD易感基因型，而携带TNF-α基因位点rs1799724 C等位基因者BPD风险较高。

Objective To explore the relationship between susceptibility loci polymorphism and bronchopul- monary dysplasia （BPD） in Han premature infants. Methods Twenty - eight susceptibility genes were speculated to be associated with BPD development according to the literature. And 46 cases of Han premature infants, who were hospitalized in Guangdong General Hospital from April to December 2013 and whose gestational age ≤ 32 weeks, birth weight （BW） ≤1500 g,were prospectively selected into the study after obtaining the informed consents from the parents. Among them,31 cases were BPD patients （BPD group） , and 15 cases were non -BPD patients （control group）. Blood samples were collected for the detection of 28 susceptibility genes within 3 days of hospitalization. After blood samples were extracted,and genomic DNA was amplified by PCR, the blood samples were then analyzed by single base extension technology and DNA mass spectrometry. Results Fourteen genes, whose frequencies were in Hardy - Weinberg equilibrium among the 28 susceptibility genes ,were finally selected as the candidate genes for the study. Tumor necrosis factor α （ TNF -α） gene rs1799724 and Toll - like receptor （TLR） - 10 gene rs11096955 were founded to be possibly related to the development of BPD. A significant higher CC [ 93.5 % （29/31 cases） ] and lower TT [ 0 （0/31 cases） contents were presented in TNF-α geue detection in BPD group,those in the control group were 33.3% （5/15 cases） ,20.0% （3/15 cases） ,and there was significant difference between 2 groups（χ^2 = 18. 044 ,P 〈 0.01 ） ;while higher AC[22.6% （7/31 cases） ] and lower CC [ 12.9% （4-/31 cases） ] contents in TLR -10 gene detection were presented in BPD group,those in the control group were 20.0% （3/15 cases） ,46.7% （7/15 cases） , there was a significant difference between 2 groups （χ^2 = 6. 252, P = 0. 043 ）. C allele distribution frequency of TNF - α gene in the BPD group [ 93.5 % （29/31 cases） ] increased, compared with that in control group [ 46.7 % （7/15 cases） ], there was a sig- nificant difference between 2 groups （χ^2 = 23. 833 ,P 〈 0.01 ）. No genetic locus was found to be related with BPD se- verity （ P 〉 0.05 ）. Conclusions TNF - α gene and TLR - 10 gene loci polymorphism might contribute to the development of BPD. TNF-α gene rs1799724 CC genotype and TLR -10 gene rs11096955 AC genotype might be the suscep- tible genotypes of BPD. TNF - α gene rs1799724 C allele carrier has a higher risk for BPD.