Preeclampsia is a gestational disorder characterized by hypertension and proteinuria. Excessive release of pro-inflammatory cytokines, particularly tumour necrosis factor-alpha, has been demonstrated to contribute to endothelial activation and poor trophoblast invasion in placental development, resulting in preeclampsia's clinical symptoms. Genetic polymorphisms of tumour necrosis factor-alpha can regulate its production and may play an important role in the pathogenesis of this disease. This study aimed to evaluate the association of five tumour necrosis factor-alpha gene promoter single nucleotide polymorphisms, or their haplotype combinations, with preeclampsia prevalence. This case-control study was conducted on 300 women with preeclampsia and 300 age-matched women with normal pregnancy from Tunisian hospitals. Genotyping of tumour necrosis factor-alpha -1031 T/C, -376 G/A, -308 G/A, -238 G/A, and +489 G/A SNPs was performed on DNA extracted from blood samples using PCR-restriction fragment-length polymorphism analysis. Statistical analysis was performed using the chi-square test. P < 0.01 were considered statistically significant to take into consideration the multiple comparisons. A significantly higher frequency of the minor allele -1031C (p < 0.001) was observed in preeclampsia cases compared to controls. Notably, the -1031C and -376A (CA) haplotype, which correlates with a higher production of TNF-α protein, had a higher incidence in women with preeclampsia (p = 0.0005). Conversely, the TG haplotype had a low frequency in preeclampsia cases compared to controls (p = 0.002) which suggests that it is associated with a reduced incidence of preeclampsia. These results suggest that tumour necrosis factor-alpha polymorphisms, in particular the -1031C/A, and the haplotype CA, contribute to an increased risk of preeclampsia in Tunisian women.

Centre de Recherche du Centre Hospitalier de l'Université de Montréal 900 St Denis Street Tour Viger R08 452 Montréal Québec H2X 0A9 Canada; School of Kinesiology and Physical Activity Sciences Université de Montréal 2100 Boul Édouard Montpetit Montréal H3T 1J4 Québec Canada

Laboratory of Human Genome and Multifactorial Diseases 900 St Denis Street Tour Viger R08 452 Montréal Québec H2X 0A9 Canada; School of Kinesiology and Physical Activity Sciences Université de Montréal 2100 Boul Édouard Montpetit Montréal H3T 1J4 Québec Canada

Laboratory of Human Genome and Multifactorial Diseases Faculty of Pharmacy of Monastir University of Monastir 5000 Street Ibn Sina Monastir Tunisia

Laboratory of Human Genome and Multifactorial Diseases Faculty of Pharmacy of Monastir University of Monastir 5000 Street Ibn Sina Monastir Tunisia; Faculty of Medicine of Sousse University of Sousse Street Mohamed Karoui 4002 Sousse Tunisia

Laboratory of Human Genome and Multifactorial Diseases Faculty of Pharmacy of Monastir University of Monastir 5000 Street Ibn Sina Monastir Tunisia; Faculty of Sciences of Bizerte University of Carthage 7021 Jarzouna Bizerte Tunisia

The 1st Faculty of Medicine and General University Hospital Institute of Biology and Medical Genetics Charles University Prague Czech Republic

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