Association of maternal and fetal cytokine genotypes with preterm deliveries

Despite the significant improvements in the prognosis of premature neonates the preterm birth (PTB) is still one of the most common cause of perinatal morbidity and mortality. Due to its multifactoral nature the pathogenic mechanism still needs to be elucidated. Although parturition involves a complex and poorly understood molecular and biological interplay between the mother and fetus the evident molecular data strogly improves the importance of the pro- and anti-inflammatory cytokines and their receptor polymorphisms those linked to matrix metabolism. In view of the location and proposed biologic effect of TNF-? and IL-1, it would be prudent to further evaluate the association between maternal ? fetal proinflammatory cytokine genotypes and PTB. The isolated genomic DNA from maternal and cord blood samples of 100 preterm and 101 term labors were used as a template. Restriction fragment size analyses were performed by examining digested PCR products for TNF-? (-238 G/A, -308 G/A), IL-1? (4845 G/T) and IL-1ß (-511 C/T) genotypes. The results of our study revealed that; TNF-? -238 GA genotype in term neonates was significantly higher than the premature neonates (p<0.05). Both maternal and fetal -238 heterozygosity was associated with term labor (p<0.05). TNF -308 GA and AA genotypes were associated with term labor (mothers and neonates respectiveley p<0,05, p<0,001) and the incidence of term labor was significantly increased in TNF-? -308 GA genotype. However when the -308 GA carrier has a fetus with GG genotype the incidance of preterm labor increases (p<0.01) 4845 T allele was significantly higher in preterm mothers and neonates (respectively p<0,001, p<0,001). The effect of maternal?fetal genotype for the pregnancy outcome revals that maternal 4845 GG ve GT genotypes increase term labor incidance, while fetal 4845 TT genotype was a significant and independent risk factor for preterm birth (p<0.01). The IL-1ß -511 TT genotype was significantly high in preterm neonates. The preterm labor risk was significantly increased in maternal -511 TT and fetal CT genotypes, while maternal -511 CT or TT genotypes have a -511 TT fetus, the insidance of term pregnancy outcome increases (p<0.01). Further research is needed to explore the usefullness of cytokine gene polymorphisms as markers of disease susceptibility (and for risk stratification) and to define their precise role in the pathogenesis of PTB.Key words: TNF-? (-238 G/A), TNF-? (-308 G/A), IL-1? (4845 G/T), IL-1ß (-511 C/T), preterm birth