DNA错配修复蛋白(MLH1,PMS2,MSH2,MSH6)与人类神经管畸形(NTDs)关联性的初步研究

A primary study on the correlation of DNA mismatch repair proteins(MLH1,PMS2,MSH2,MSH6) with neural tube defects(NTDs)

目的通过观察神经管畸形(Neural Tube Defects,NTDs)患儿与正常胎儿脑组织中DNA错配修复(mis-match repair,MMR)蛋白MLH1、PMS2、MSH2及MSH6的表达情况,探讨MMR系统与NTDs发生机理间可能存在的联系。方法 NTDs患儿脑组织及正常胎儿脑组织各15例,运用免疫组化方法检测各病例中MLH1、PMS2、MSH2及MSH6蛋白表达情况。结果 NTDs组MLH1阳性率中位数为1.44%,正常组为(41.96±11.01)%,中位数为43.95%;NTDs组PMS2阳性率为(25.48±16.46)%;正常组为(43.36±7.86)%。NTDs组中两种蛋白较正常组明显下降,组间存在统计学差异(P<0.01)。但NTDs组中MSH2及MSH6阳性率分别为(43.56±18.67)%、(32.26±23.18)%;正常组中为(45.87±8.49)%、(35.15±10.68)%。两种蛋白组间比较无统计学差异,P值分别为0.6516和0.5387。结论首次报道NTDs中可能存在一种或多种特定MMR蛋白表达异常,推测MMR系统表达异常可能在NTDs发生过程中起到重要作用。

Objective： To investigate the possible correlation of DNA mismatch repair （MMR） system with the pathogenesis of neural tube defects （ NTDs）, we observed the expression of MMR proteins MLH1, PMS2, MSH2 and MSH6 in brain tissues of NTDs and normal embryos respectively. Methods ： Immunohistochemistry was used to evaluate the expression of MMR proteins （ MLH1, PMS2, MSH2 and MSH6） in NTDs and normal groups, which contained 15 cases for each. Results： It was observed that MLH1 positive rate was 1.44% （median） in NTDs group and 43.95% （median） in the normal. Meanwhile, PMS2 positive rate was （25.48± 16. 46）% in NTDs group and （43.36%±7. 86）% in the normal. MLH1 and PMS2 proteins decreased in NTDs group, and statistic analysis indicated both proteins had significant differences （ P 〈0.01 ） between the two groups. However, in NTDs group, MSH2 and MSH6 positive rates were （43.56 ± 18. 67）% and （32.26 ±23.18）% respectively, and in the normal group, they were （45.8± 28.49）% and （35.15± 10. 68）%. For both proteins, no significant difference was found between the two groups. P value was 0. 6516 for MSH2 and 0. 5387 for MSH6. Conclusions： It was the first report about that the decreased expression of single or multiple specific MMR proteins could probably exist in NTDs, and we postulated that this kind of abnormal expression of MMR proteins possibly played a significant role in NTDs＇ pathogenesis.