Preeclampsia in North Indian women: the contribution of genetic polymorphisms

Aim: To find association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) T704C, methylenetetrahydrofolate reductase (MTHFR) C677T and factor V Leiden (FVL) G1691A polymorphisms with pre-eclampsia (PE) in North Indian women. Material & Methods: In this prospective case-control study, genotyping of 200 pre-eclamptic women and 200 normotensive pregnant controls was performed for the ACE I/D, AGT T/C, MTHFR C/T and FVL G/A polymorphisms. Statistical analysis was carried out using SPSS and Epi Info to estimate their association with PE. The association of these polymorphisms with nonsevere PE and severe PE was separately assessed. Results: The FVL mutation was found in 4% of women and increased the risk of PE twofold (odds ratio [OR] 2.08, P-value 0.03). The MTHFR mutant allele was found to be protective (OR 0.59, P-value 0.01). Both these polymorphisms showed similar association with nonsevere PE (OR 2.149, P-value 0.038 and OR 0.565, P-value 0.222, respectively) but not with severe PE. The ACE I/D and AGT T/C polymorphisms were not found to be associated with PE overall (OR 1.26, P-value 0.11 and OR 1.15, P-value 0.35, respectively), but ACE I/D polymorphism was found to increase the risk of severe PE (OR 1.53, P-value 0.019). Conclusion: FVL mutation is more common in North Indians than previously believed and it predisposes the women to PE. MTHFR mutant allele is paradoxically protective. ACE polymorphism appears to predispose to severe PE but not nonsevere PE. No significant contribution of AGT polymorphism to PE is found.