342. Association between Tumor Necrosis Factor Alpha (TNF-α) polymorphisms and haplotypes and preeclampsia risk

Introduction Preeclampsia is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Excessive release of pro-inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-α) has been demonstrated to contribute to endothelial activation and default of trophoblasts invasion that result in the clinical symptoms of preeclampsia. Genetic polymorphisms of TNF-α could regulate its production and may play an important role in the pathogenesis of this disease. Objective/hypothesis The aim of this study was to evaluate the association of five different TNF-α gene promoter single nucleotide polymorphisms (SNPs), or their haplotype combinations, with the development of preeclampsia. Methods This a case-control study conducted on 300 women with PE and 300 age-matched women with normal pregnancy from Tunisian hospitals. Genotyping of TNF-α −1031T/C, −376G/A, −308G/A, −238G/A, and  + 488C/T SNPs was performed on DNA extracted from blood samples. TNF-α genotyping was assessed using PCR-restriction fragment-length polymorphism (RFLP) analysis. Statistical analysis was performed using the chi-square test. P values less than 0.01 were considered statistically significant. Results Our results demonstrated a higher frequency of the minor allele  − 1031C (p  ⧹ A is associated with lower systolic blood pressure while the minor allele is associated with increased diastolic blood pressure. Discussion These results demonstrate that TNF-α polymorphisms, in particular  − 1031C/A and  − 376 G/A, are significantly associated with preeclampsia. In addition, we found a protective effect of the major allele G of  − 308 G ⧹ A SNP on systolic blood pressure while increased diastolic blood pressure can be found in carriers of the minor allele A.