一项关于编码细胞因子（IL6、IL10、TNF）、细胞因子受体（IL6R、IL6ST）和糖皮质激素受体（NR3C1）的基因与支气管肺发育不良易感性的研究。
A study of genes encoding cytokines (IL6, IL10, TNF), cytokine receptors (IL6R, IL6ST), and glucocorticoid receptor (NR3C1) and susceptibility to bronchopulmonary dysplasia.
作者信息
Huusko Johanna M, Karjalainen Minna K, Mahlman Mari, Haataja Ritva, Kari M Anneli, Andersson Sture, Toldi Gergely, Tammela Outi, Rämet Mika, Lavoie Pascal M, Hallman Mikko
机构信息
Department of Pediatrics, Institute of Clinical Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
出版信息
BMC Med Genet. 2014 Nov 1;15:120. doi: 10.1186/s12881-014-0120-7.
BACKGROUND
Bronchopulmonary dysplasia (BPD) is a common chronic lung disease associated with very preterm birth. The major risk factors include lung inflammation and lung immaturity. In addition, genetic factors play an important role in susceptibility to moderate-to-severe BPD. In this study, the aim was to investigate whether common polymorphisms of specific genes that are involved in inflammation or differentiation of the lung have influence on BPD susceptibility.
METHODS
Genes encoding interleukin-6 (IL6) and its receptors (IL6R and IL6ST), IL-10 (IL10), tumor necrosis factor (TNF), and glucocorticoid receptor (NR3C1) were assessed for associations with moderate-to-severe BPD susceptibility. Five IL6, nine IL6R, four IL6ST, one IL10, two TNF, and 23 NR3C1 single nucleotide polymorphisms (SNPs) were analyzed in very preterm infants born in northern Finland (56 cases and 197 controls) and Canada (58 cases and 68 controls). IL-6, TNF and gp130 contents in umbilical cord blood, collected from very preterm infants, were studied for associations with the polymorphisms. Epistasis (i.e., interactions between SNPs in BPD susceptibility) was also examined. SNPs showing suggestive associations were analyzed in additional replication populations from Finland (39 cases and 188 controls) and Hungary (29 cases and 40 controls).
RESULTS
None of the studied SNPs were associated with BPD nor were the IL6, TNF or IL6ST SNPs associated with cord blood IL-6, TNF and gp130, respectively. However, epistasis analysis suggested that SNPs in IL6ST and IL10 were associated interactively with risk of BPD in the northern Finnish population; however, this finding did not remain significant after correction for multiple testing and the finding was not replicated in the other populations.
CONCLUSIONS
We conclude that the analyzed SNPs within IL6, IL6R, IL6ST, IL10, TNF, and NR3C1 were not associated with BPD. Furthermore, there was no evidence that the studied SNPs directly contribute to the cord blood protein contents.
背景
支气管肺发育不良（BPD）是一种与极早早产相关的常见慢性肺部疾病。主要危险因素包括肺部炎症和肺不成熟。此外，遗传因素在中重度BPD易感性中起重要作用。在本研究中，目的是调查参与肺部炎症或分化的特定基因的常见多态性是否对BPD易感性有影响。
方法
评估编码白细胞介素-6（IL6）及其受体（IL6R和IL6ST）、白细胞介素-10（IL10）、肿瘤坏死因子（TNF）和糖皮质激素受体（NR3C1）的基因与中重度BPD易感性的关联。对芬兰北部出生的极早早产儿（56例病例和197例对照）和加拿大出生的极早早产儿（58例病例和68例对照）分析了5个IL6、9个IL6R、4个IL6ST、1个IL10、2个TNF和23个NR3C1单核苷酸多态性（SNP）。研究了从极早早产儿采集的脐带血中IL-6、TNF和gp130含量与这些多态性的关联。还检查了上位性（即BPD易感性中SNP之间的相互作用）。在来自芬兰（39例病例和188例对照）和匈牙利（29例病例和40例对照）的额外重复人群中分析显示有提示性关联的SNP。
结果
所研究的SNP均与BPD无关，IL6、TNF或IL6ST的SNP也分别与脐带血IL-6、TNF和gp130无关。然而，上位性分析表明，IL6ST和IL10中的SNP在芬兰北部人群中与BPD风险存在交互关联；然而，在多重检验校正后这一发现不再显著，且该发现在其他人群中未得到重复验证。
结论
我们得出结论，IL6、IL6R、IL6ST、IL10、TNF和NR3C1内分析的SNP与BPD无关。此外，没有证据表明所研究的SNP直接影响脐带血蛋白质含量。
Zotero 插件