Association between IL-6–174 (G/C) polymorphism and cystic periventricular leukomalacia in preterm infants

Background: The fetal inflammatory response syndrome plays a central role in the pathogenesis of white matter damage, i.e. cystic periventricular leukomalacia (PVL) in the preterm infant. High levels of proinflammatory cytokines including interleukin-6 (IL-6) have been observed in autopsies of brains of these infants. Thus, an association between IL-6–174 (G/C) polymorphism, affecting IL-6 transcription rate and plasma cytokine levels, and development of PVL might be hypothesized.

Patients and methods: The study group (cases) compromised infants with diagnosis of cystic PVL out of a single centre cohort from 1988 to 2005 and their parents. The control group (controls) included healthy newborns born between April and June 2002. Analysis of IL-6–174 (G/C) polymorphisms was performed in cases and their parents from venous blood samples after parental informed consent and in controls from umbilical cord blood samples. Samples were stored at -200 degree Celsius. IL-6 genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The study was approved by the local ethic committee.

Results: Fifty-two cases (and 44 mothers) were enrolled and compared to 395 controls. Rates of homozygous carrier of the IL-6–176C mutation were 17,3% in the cases, 15,9% in their mothers and 14,7% in the controls (differences not significant). Again no differences were found in the subgroup of cases with history of premature rupture of the membranes (PROM) or chorioamnionitis. An increased rate was found in mothers of cases with history of chorioamnionitis (7/23, 30,4%; p=0,0192).

Conclusion: We found a significant increased rate of homozygous carriers of the IL-6–176C mutation in mothers with chorioamnionitis and preterm birth with subsequent development of cystic PVL. In case of preterm PROM knowledge of this polymorphism might influence timing of delivery.