Association of maternal Toll-like receptor-4 alleles with susceptibility to early-onset preeclampsia in central Greece

Abstract

Introduction: Altered maternal inflammatory responses may play a role in the development of hypertensive disorders of pregnancy like preeclampsia, its more severe early-onset form and intrauterine growth restriction. We evaluated the relation of common allelic variants of Toll-like receptor 4 (TLR4), known to impair the inflammatory response, with the susceptibility to early-onset preeclampsia in Central Greece.

Methods: We compared the occurrence of TLR4 (Asp299Gly and Thr399Ile) alleles in heterozygous (A/G, C/T) and homozygous (G/G, T/T) states in 84 women with a history of early-onset preeclampsia and 94 age matched controls with a history of only uneventful pregnancies, by direct sequencing.

Results: Heterozygous TLR4 allelic variants were more common in women with a history of early-onset preeclampsia than in controls (GA for Asp299Gly: 14.3% vs 6.4% (AA), p = 0.053 & CT for Thr399Ile: 16.7% vs. 6.4% (CC), p = 0.019) and a stronger association was obtained when homozygous allelic carriers were also included (GA/GG for Asp299Gly: 16.7% vs. 6.4% (AA), p = 0.03 & TC/TT for Thr399Ile: 19.0% vs. 6.4% (CC), p = 0.01).

Discussion: We recorded association between common TLR4 gene variants and early-onset preeclampsia. Our findings support the involvement of maternal innate immune system in severe hypertensive disorders of pregnancy and point to the potential value of maternal TLR4 polymorphisms as predictors-risk factors of susceptibility to early-onset preeclampsia in Central Greece.

Keywords: Early-onset preeclampsia; Gene polymorphism; TLR4.