血管内皮生长因子基因多态性与早产儿视网膜病变发病和预后的关系

Relationship of vascular endothelial growth factor gene polymorphisms with retinopathy of prematurity in pre-term infants

背景不同早产儿个体之间对早产儿视网膜病变（ROP）发病易感性的差异较大，可能与血管内皮生长因子（VEGF）基因多态性有关。目的研究ROP患儿VEGF基因多态性的表型，探讨VEGF基因多态性与ROP的关系。方法采用前瞻性系列病例对照研究设计，纳入2006年1月至2009年12月在湖南省儿童医院新生儿科住院的1～5期ROP患儿99例作为ROP组，另纳入80例同期未发生ROP的早产儿为对照无ROP组；在ROP组中将行激光或冷冻治疗的患儿39例作为治疗组，同期未经治疗ROP自发消退的患儿60例作为非治疗组。ROP组与无ROP组间、治疗组与非治疗组问的人口基线学特征比较差异均无统计学意义（P〉0．05）。抽取各组患儿外周血2ml以提取DNA，利用焦磷酸测序法进行VEGF—A＋405、VEGF—A936基因的多态性研究。结果ROP组患儿与无ROP组患儿VEGF—A＋405基因表型的差异均无统计学意义（P=0．071，OR=0．675，95％c，=0．444～1．026）。ROP组患儿与无ROP组患儿VEGF—A936基因表型的差异亦无统计学意义（P=0．118，OR=0．768，95％CI为2．823～4．614），但治疗组与非治疗组VEGF—A＋405，VEGF—A936基因多态性表型的差异均有统计学意义（VEGF—A＋405：P〈0．01，OR=0．875，95％C1为5．239～14．024；VEGF—A936：P=0．000，OR=3．609，95％CI为0．711～0．829）。结论VEGF—A＋405和VEGF—A936基因的多态性与ROP易感性无关，但与ROP预后有关。携带VEGF—A＋405、VEGF—A936等位基因可能增加ROP进展的风险。

Background Statistic data revealed that different retinopathy of pre-term infants have different susceptibility to retinopathy of prematurity （ROP） ,which may be associated with polymorphism of vascular endothelial growth factor（VEGF） gene. Objective This study was to determine the association of polymorphisms of VEGF gene with the risk for ROP. Methods This research was approved by Ethics Committee of Hunan Children＇s Hospital,and written informed consent was obtained from the parents of patients. A prospective case-controlled study was designed. Ninety-nine ROP patients in Hunan Children＇ s Hospital and 88 pre-termed children without ROP were included from January, 2006 to December, 2009. Thirty-nine patients who received retinal photocoagulation or cryotherapy were included as the treatment group,and 60 untreated but spontaneously regressed ROP patients as the non-treatment group. No significant differences were seen in demography between with the ROP group and the without ROP group,or between the treatment group and the non-treatment group （all P〉0.05 ）. 2 mL of peripheral blood was collected for the extraction of DNA. Gene polymorphisms of VEGF-A＋405 and VEGF-A936 were detected using the pyrosequencing method. Results No significant difference was found in the frequencies of the VEGF-A＋405 gene polymorphisms between the ROP group and without ROP group （ P = 0. 071, OR = 0. 675,95% CI = 0. 444-1. 026 ）. Also no significant difference was found in the frequencies of the VEGF-A936 gene polymorphisms between with the ROP group and without the ROP group （ P = 0. 118, OR = 0. 768,95 % CI = 2. 823-4. 614 ）. However, the frequencies of the VEGF-A ＋405 gene polymorphisms were significantly higher in the ROP treatment group than the non-treatment group （ P〈0. 01, OR = 0. 857,95 % CI = 5. 239 - 14. 024 ） , and VEGF-A936 gene polymorphisms was also significantly higher in the ROP treatment group than the non-treatment group （P = 0. 000, OR = 3. 609,95 % CI = 0.711-0. 829 ）. Conclusions There is no association between the VEGF-A＋405/VEGF-A936 single nucleotide polymorphism with the risk of ROP,but polymorphisms of VEGF gene may be correlated with the prognosis of ROP. The carrier of VEGF-A ＋405 /VEGF-A936 allele is more susceptible to ROP progression.