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MUltiplex Measurement of Cytokine/Receptor Gene Polymorphisms and interaction Between Interleukin-10 (-1082) Genotype and Chorioamnionitis in Extreme Preterm Delivery

Michael Dördelmann, MD

Dorothee B. Bartels, PhD

Maria-Jantje Brinkhaus

Christiane E. L. Dammann, MD

Thilo Dörk, PhD

Department of Gynecology and Obstetrics, Department of Pediatric Pulmonology and Neonatology, and Perinatal Infectious Disease Epidemiology Unit, Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany; Department of Pediatrics, Division of Newborn Medicine, Floating Hospital, tufts University, Boston, MA; Neuroepidemiology Unit, Departments of Neurology, Children's Hospital and Harvard Medical School, boston, MA

Olaf Dammann, MD

Department of Gynecology and Obstetrics, Department of Pediatric Pulmonology and Neonatology, and Perinatal Infectious Disease Epidemiology Unit, Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany; Department of Pediatrics, Division of Newborn Medicine, Floating Hospital, tufts University, Boston, MA; Neuroepidemiology Unit, Departments of Neurology, Children's Hospital and Harvard Medical School, boston, MA dammann.olaf{at}mh-hannover.de

Objectives: To establish a multiplex amplification refractory mutation system (ARMS) in fluid and dried whole blood, and to perform a pilot study to examine the role for single-uncleotide polymorphisms (SNPs) of inflammation-sassociated genes (interleukin [Il]-1 and -10, tumor necrosis factor-alpha [TNFA], and toll-like receptor-4 [TLR4]) and their interaction with clinical chorioamnionitis (CAM) in prematurity.

Methods: We established a quadruplex ARMS to detect the four above SNPs. Fifty-four women delivered at gestational age less than 32 weeks and 83 healthy female volunteers were genotyped. We compared (1) mothers of preterm infants with volunteers, and (2) women delivered before 29 weeks' gestation (n = 29) with those delivered at 29 to 31 completed weeks (n = 25).

Results: Multiplex ARMS is feasible using both fluid and dried whole blood. We found no overall differences in genotype and allele frequencies between mothers of preterm infants and volunteers. Among women who had a preterm delivery, those with both CAM and IL10(- 1082)* G allele, the risk for delivery before 29 weeks was markedly increased (odds ratio [OR] 22, 95% confidence interval [CI] 2.5 - 191).

Conclusion: The presence of both CAM and IL10(- 1082)* G might play a role in extreme preterm delivery less than 29 weeks.

Key Words: Cytokines • polymorphisms • chorioamnionitis • prematurity

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 5, 350-356 (2006)
DOI: 10.1016/j.jsgi.2006.04.004


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