Polymorphisms of genes involved in innate immunity: association with preterm delivery

Abstract

An altered inflammatory activity due to functionally relevant polymorphisms of the innate immune system may influence pathways leading to labour and, therefore, impact on the frequency of preterm birth. We examined five polymorphisms of the innate immune system in a large cohort of preterm very-low-birth-weight (VLBW, n = 909) and term-born infants (n = 491) and their mothers (n = 747). The primary outcome was preterm versus term birth. Frequencies of polymorphisms in mothers of term-born infants versus mothers of VLBW infants and term infants versus preterm VLBW infants (singletons) are given. Homozygous CD14-159T: 18.5 versus 21.8% (mothers) and 19.6 versus 21.2% (infants). Homozygous interleukin IL-6-174G: 28.8 versus 38% (P = 0.018, mothers) and 30 versus 32.7% (infants). Homozygous or heterozygous nuclear oligomerization domain NOD2-3020insC: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Heterozygous or homozygous toll-like-receptor TLR2-Arg753Gln: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Homozygous or heterozygous TLR4-896G: 8.1 versus 11.5% (mothers) and 11.6 versus 10.5% (infants). Although the homozygous maternal IL-6-174G genotype was found to be independently associated with preterm delivery in multivariate regression analysis, the incidence of intrauterine infection was not significantly increased in mothers of preterm VLBW-infants, carrying this or other polymorphisms of the innate immune system. The overall influence of the investigated polymorphisms on the development of preterm delivery seems moderate, since only the maternal IL6-174G genotype was associated with preterm birth and none of the polymorphisms were associated with intrauterine infection as the cause of preterm birth.

Study of disease-relevant polymorphisms in the TLR4 and TLR9 genes: A novel method applied to the analysis of the Portuguese population

“…In addition and as expected, both TLR4 polymorphisms are in total linkage disequilibrium (D 0 ¼ 1.000). In fact, cosegregation among these two mutations has also been largely stated [13,30,31].…”

Ethnic differences in interleukin 6 (IL‐6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels

“…For these reasons, IL-6 is considered a "marker" of high risk status for PTB (Romero et al 1993). In addition, genetic association studies demonstrated that a single nucleotide polymorphism (SNP) in the promoter region of the IL6 gene (C-174G) decreases promoter activity, and the (G/G) homozygote associates with increased risk of PTB (Hartel et al 2004). IL6, as well as the gene encoding its receptor (IL-6 receptor IL6R), through which IL-6 mediates its biological function, are therefore strong candidates for PTB and perhaps for the ethnic disparity in PTB.…”

Common Oxytocin Receptor Gene Polymorphisms and the Risk for Preterm Birth

“…Therefore in modern obstetric practice, oxytocin is widely used to induce and augment contractions during labor [28]. Furthermore, associations between several maternal gene polymorphisms, such as tumor necrosis factor, interleukin (IL)-4, IL-1ß receptor antagonist, matrix metalloproteinase 9, ß2-adrenergic receptor, vascular endothelial growth factor and for Factor V Leiden [11] and PTB have been described. Consequently, we speculated that OXTR gene polymorphisms might also play a role in PTB and to the best of our knowledge are the first to have investigated association of OXTR single nucleotide polymorphisms rs2254298, rs53576, rs2228485, rs237911 and PTB.…”