TNFα启动子基因多态性与子痫前期的相关研究

A study on relationship between promoter gene polymorphisms of TNFα and pre-eclampsia

目的探讨TNFα-308、TNFα-238启动子基因多态性与子痫前期的易感性及其严重程度的相关性。方法检测37例子痫前期孕妇(其中轻度子痫前期15例,重度子痫前期22例)、84例正常孕妇TNFα的血清学表达及测定TNFα-308、TNFα-238的多态性。并对TNFα基因型及不同基因型编码的细胞因子的血清浓度进行统计学分析。结果TNFα-308GG在子痫前期患者中的分布频率低于对照组(P<0.05,OR=0.22),TNFα-308GA在子痫前期患者中的分布频率高于对照组(P<0.05,OR=4.07),TNFα-308AA在子痫前期患者中发现2例,正常孕妇仅发现1例。TNFα-308各基因型在轻度、重度子痫前期患者中的分布频率无显著性差异。TNFα-238位点突变率低,在两组中的分布无显著性差异(P>0.05)。不同基因型TNFα血清学的表达不同:携带GA+AA基因型患者TNFα血清值高于GG基因型者(4.29±0.40vs3.26±0.62,t=-4.83,P<0.05)。结论TNFα-308的多态性影响其编码的细胞因子的表达,可能与子痫前期的发病相关。

Objective To investigate relationship between TNFα promoter gene polymorphisms and susceptibility, severity of preeclampsia. Methods Thirty-seven patients with pre-eclampsia （ including 15 cases of mild pre-eclampsia and 22 cases of severe preeclampsia, as the study group） and eighty-four normal pregnant women （as the control group） were examined for serological examination of TNFα and their TNFα-308, TNFα-238, SNPs were genotyped by PCR-RFLP. Serum levels of gynotypes of TNFα and cytokines coded by different gynotypes were analyzed statistically. Results The frequency of TNFα-308GG genotype was significantly lower in the pre-eclampsia women group than that in the control group （P 〈0. 05, OR =0. 22 ）, while that of TNFα-308GA genotype was significantly higher in the pre-eclampsia women group compared with the control group （P 〈 0. 05, OR = 4.07 ）. TNFα-308AA genotype was found in 2 women with pre-eclampsia and 1 normal woman, In frequencies of different TNFα genotypes, there were no significant differences between mild and severe pre-eclampsia of women. The mutation freguency of promoter gene of TNFα at the 238 locus was lower and there was no significant difference between the two groups （P 〈 0. 05）. The serological expression of different TNFα genotypes varied：the serum level of TNFα of pre-eclampsia women with TNFα-308 （ GA ＋ AA） allele was significantly higher than that of pre-eclampsia women with TNFα-308 GG allele （4.29 ± 0. 40 vs 3.26 ±0. 62, t = -4.83, P 〈 0. 05）. Conclusion The genotype polymorphisms of TNFα-308 influence the expression of cytokines coded by them, which may be related with development of pre-eclampsia.