Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women

Abstract

Objective: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preeclampsia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preeclamptic women.

Methods: One hundred seventy-five nulliparous Sinhalese women with preeclampsia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preeclampsia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system.

Results: The prevalence of the CT genotype of IL1A rs17561 polymorphism was increased in preeclamptic women compared with controls {p = 0.04, odds ratio (OR) [95% class interval (CI)] = 1.6 (1.0–2.5)}. The prevalence of the CT genotype [p = 0.01, OR (95% CI) = 1.8 (1.1–2.8)] and the dominant model (CT + TT) [p = 0.03, OR (95% CI) = 1.6 (1.1–2.5)] of the IL1A rs1800587 polymorphism were increased in preeclamptic women compared with controls. The prevalence of the GA genotype [p = 0.04, OR (95% CI) = 0.6 (0.4–0.9)] and the dominant model (GA + AA) [p = 0.03, OR (95% CI) = 0.6 (0.4–0.9)] of the MBL1 rs1800450 polymorphism were reduced in preeclamptic women compared to controls.

Conclusion: Genotypes conferring a pro-inflammatory phenotype are increased in preeclamptic women.

• Inflammation
• interleukin
• polymorphism
• preeclampsia

Acknowledgements

We wish to thank the women who generously consented to participate in this study.

The contributions made by Professor Fiona Brought Pipkin and Dr. Linda Morgan to the establishment of the sample collection is acknowledged.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This study was funded by the National Health and Medical Research Council Australia (NHMRC) Project Grant ID519225 awarded to CTR and GAD. C.T.R. is supported by a NHMRC Senior Research Fellowship (GNT1020749). P.H.A. is supported by a NHMRC Peter Doherty Postdoctoral Fellowship (GNT1090778). The recruitment, characterization and establishment of the preeclampsia sample collection in Sri Lanka was funded by a PhD studentship held by VHWD at the University of Nottingham, UK, from 2001 to 2004 funded by the President's Fund Sri Lanka, University of Colombo, Sri Lanka and the University of Nottingham, UK. The study sponsors had no role in study design, data analyses, and interpretation or writing this report.