Importance of polymorphic variants of Tumour Necrosis Factor - α gene in the etiology of Intrauterine Growth Restriction

Abstract

Objectives: Intrauterine growth restriction (IUGR) is one of the main global causes of increased perinatal mortality and fetal and neonatal morbidity. It remains a key challenge for modern perinatal medicine. Negative effects of IUGR are manifested not only in the perinatal period but also at the later stages of life. Proinflammatory cytokines and their polymorphisms are hypothesized to play an important role in IUGR pathomechanisms. The aim of the study was to determine the role of selected polymorphisms (-238G > A, -308G > A and -376G > A) of tumor necrosis factor alpha (TNF-α) in the etiology of intrauterine growth restriction. Material and methods: The study included 120 patients with IUGR (mean age 30.32, mean gestational age 36.34 gestational weeks) and 135 healthy pregnant women (mean age 31.63, average week of delivery 38.76). The investigated polymorphisms were determined by PCR/RFLP methods. Results: Higher frequency of TNF-α mutated allele -308A was found in a subgroup of women whose pregnancy ended < 37 weeks (18.5 vs. 12.2% in control, OR = 1.63, p = 0.09) and in the subgroup of women with a score ≥ 3 UAS (20.6 vs. 12.2% in control, OR = 1.86, p = 0.06). Heterozygous genotype -308GA was associated with at least 3 times greater risk of three or four abnormalities in uterine arteries score (41.2 vs. 20.0 in control, OR = 2.80, p = 0.01). Conclusions: The obtained results suggest that the -308G > A TNF-α gene variant may play a role in the etiology of IUGR in the Polish population, but further studies on larger groups are needed.