Promoter hypomethylation of TIMP3 is associated with pre-eclampsia in a Chinese population

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Abstract

A study by Yuen RK, Penaherrera MS, von Dadelszen P, McFadden DE, Robinson WP. DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia. Eur J Hum Genet 2010;18:1006–1012 based on a Canadian population found the tissue inhibitor of the metalloproteinase 3 (TIMP3) gene to be hypomethylated in pre-eclampsia (PE) placentas and to be a potential prenatal marker for early onset PE. To further explore the role of TIMP3 in PE and to investigate whether the TIMP3 promoter shows the same methylation pattern in the Han Chinese population, we analyzed a complete methylation assay of TIMP3 including the promoter region studied in the Canadian report and the neighboring CpG island in placentas (cases n = 41, controls n = 22) maternal peripheral blood (cases n = 3; controls n = 6) and umbilical cord blood (cases n = 7; controls n = 8) using MassArray EpiTyper (Sequenom, San Diego, CA, USA). Our results confirmed the finding of aberrant TIMP3 promoter methylation in PE placentas (mean = 0.405) compared with those in controls (mean = 0.534, P = 9.40 × 10−7). A tissue-specific methylation pattern between placentas (mean = 0.459) and bloods (mean = 0.961, P = 6.91 × 10−13) was also demonstrated in our clinical samples. Furthermore, a nearly 2-fold increase in TIMP3 expression for the hypomethylated promoter was found in PE placentas (P = 0.007), pointing to a negative relationship between TIMP3 methylation and the expression (R = −0.758, P = 0.029). In conclusion, we replicated the findings of Yuen et al. in our Han Chinese-based study, confirming that TIMP3 is likely to be involved in the etiology of PE and that hypomethylated and placenta-specific TIMP3 may be a potential marker for early diagnosis of PE in maternal plasma.

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