先天性心脏病肺动脉高压与血管内皮生长因子水平及基因多态性相关研究

目的探讨血管内皮生长因子（VEGF）以及VEGF 936C／T基因多态性与先天性心脏病（先心病）肺动脉高压（PH）之间的关系。方法应用ELISA方法测定左向右分流型先心病PH患儿组、不伴PH患儿组和正常对照组血清VEGF浓度；运用PCR-RFLP技术分析3组VEGF 936C／T基因频率。结果①先心病PH组血清VEGF浓度明显高于不伴PH组和正常对照组（P〈0．05），先心病不伴PH组与正常对照组比较差异无显著性，中、重度PH组血清VEGF浓度明显高于轻度PH组（P〈0．05）；②3组VEGF 936C／T基因多态性比较，差异无显著性（P〉0．05）；③3组CT型血清VEGF浓度明显低于CC型，差异均有显著性（P〈0．05）。结论VEGF在先心病PH形成和进展过程中有一定的介导作用。VEGF 936T等位基因血清VEGF浓度有偏低倾向。VEGF 936C／T基因多态性可能不是先心病PH的主要基因危险因素．有待大样本量进一步证实。

Role of vascular endothelial growth factor and its gene polymorphisms in the pathogenesis of secondary pulmonary hypertension caused by congenital heart disease

Objective To explore the role of vascular endothelial growth factor (VEGF) and VEGF polymorphisms in the pathogenesis of secondary pulmonary hypertension (PH) caused by congenital heart disease (CHD). Methods The type of CHD with left to right shunt was differentiated by echocardiography. The grade of PH was defined that the mean pulmonary artery pressure (MPAP) was 21 - 30 mmHg as mild PH, 31- 50 mmHg as moderate PH, and >50 mmHg as severe PH, respectively. Serum VEGF concentration with enzyme-linked immunosorbent assay was detected in 27 children with CHD complicating PH (PH group), 21 children with CHD non-complicating PH (non-PH group) and 25 healthy control subjects (control group), respectively. DNA genome was extracted from peripheral blood leucocytes, and polymerase chain reaction (PCR) was employed to amplify a 208bp fragment in exon 8 including 936 C/ T mutation in 3' untranslated region of the VEGF gene. The frequency of VEGF 936 C/ T genotype was analyzed with the method of restriction fragment length polymorphism (RFLP) in all children of three groups. Results (1) The level of serum VEGF in PH group was significantly higher than those in either non-PH or control groups (F<0.05 for both) . There was no significant difference in the level of serum VEGF between latter two groups (P>0.05) . (2) The level of serum VEGF was significantly higher in moderate to severe PH group than that in mild group (P<0. 05). (3) No significantly difference in the frequency of VEGF 936C/T genotype was observed among PH group, non-PH group and control group (P> 0.05 for all) . (4) The level of serum VEGF in CC genotype was significantly higher than that in CT genotype among all children of three groups (P<0.05 for all). Conclusions It is suggested that VEGF probably plays an important role in the formation and progress of PH in children with CHD. VEGF 936T allele seems to lead to lower level of serum VEGF. However, the correlation between the polymorphisms of VEGF 936C/T genotype and the pathogenesis of secondary PH caused by CHD remained unknown, further investigation with a larger sample size will be required.