Genetic variants in pre-eclampsia should be interpreted with caution.

Genetic variants in pre-eclampsia should be interpreted with caution Sir, We read the article entitled 'Genetic variants in pre-eclampsia: a meta-analysis' by Buurma et al. (2013) with great interest. It is an important step forward in the identification of genetic variants associated with pre-eclampsia. However, there are several important issues that require clarification or further research. First, according to the value of I 2 , some studies included in the meta-analysis had notable heterogeneity (e.g. AGT rs699 and SERPINEI rs1799889). Apart from the sample size, many factors (e.g. linkage dis-equilibrium, ethnicity and study quality) may cause the between-study heterogeneity. Rather than simply product a combined estimate of effect, we should explore the potential methodological reasons for heterogeneity by meta-regression or sensitivity analysis (Khoury and Little, 2000). Without these data, it is not appropriate to draw conclusions about the 'true associations' between gene variants and pre-eclampsia. Secondly, the potential influence of ethnicity was not clarified clearly. Even though the overall effect of AGT (rs699) on pre-eclampsia risk was not significant, subgroup analysis showed the mutation of AGT (rs699) significantly increased the risk in Caucasians but not in Asians (Ni et al., 2012). Similarly, opposite to the overall null association, we found a positive association between MTHFR (rs1801133) mutation and pre-eclampsia when restricted to Asian population, which was also demonstrated by Xia et al. (2012). We suggest exploring the inconsistencies in specific populations and reporting detailed data for meta-analysis to avoid causing confusion. Finally, we compared the results of Buurma et al. (2013) with a similar meta-analysis (Staines-Urias et al., 2012). Including one more original study of SERPINEI (rs1799889) than Buurma et al., Staines-Urias et al. (n ¼ 12) came into a different conclusion (OR, 0.89; 95% CI, 0.73 –1.09). Although the change in statistical significance may be due to the exclusion of large sample-size study, the results of the meta-analysis should really be interpreted with caution. In addition, few single candidate genes of pre-eclampsia have been confirmed by Genome-wide association studies (GWAS) up to date. Since pre-eclampsia is a set of multi-factorial syndromes (Steegers et al., 2010), combining GWAS with gene–environment interaction studies (Thomas, 2010) may provide a more comprehensive sight into pre-eclampsia. contributes to risk of preeclampsia: evidence from a meta-analysis. Reply: Genetic variants in pre-eclampsia should be interpreted with caution Sir, We would like to thank the authors for their valuable remarks. In their letter, the authors first mention …