Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes.

INTRODUCTION

Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD). Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM. The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A, ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM.

DESIGN

Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224-288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-restricted fragment length polymorphism or sequence specific primer assays.

RESULTS

For all loci, genotype distribution was in agreement with Hardy-Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls). Analysis of two-locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50% vs. 40% in controls).

CONCLUSIONS

Physically unlinked genes involved in RAS segregate independently. The AGT 174-235 region is associated with PD-PRM in this population.