A study of collectin genes in spontaneous preterm birth reveals an association with a common surfactant protein D gene polymorphism.

INTRODUCTION: Preterm birth is the major cause of mortality and morbidity in neonates. Intrauterine infection and/or inflammatory response are evident in 60-70% of spontaneous preterm births (SPTBs). Genetic factors significantly increase this risk. However, the genetic background associated with SPTB is poorly understood. Surfactant protein (SP) A, SP-D, and mannose-binding lectin (MBL) are structurally and functionally related collectins that bind pathogen-associated molecular patterns, and mostly suppress innate immune responses.

RESULTS: We detected an overrepresentation of the methionine allele of the SFTPD gene (encoding SP-D) Met31Thr polymorphism in preterm infants as compared to term infants. This association was highly significant in infants of families with recurrent SPTBs (P = 0.001, odds ratio = 1.65, 95% confidence interval = 1.22-2.22); however, there was no such association with SFTPD in the mothers of these infants. Polymorphism of the genes encoding SP-A and MBL did not influence the risk of SPTB.

DISCUSSION: Our results suggest that the fetal SFTPD Met31Thr polymorphism plays a significant role in genetic predisposition to SPTB. We propose that fetal immune responses influence sensitivity to preterm labor-inducing signals.

METHODS: Genes encoding SP-A, SP-D, and MBL were investigated as potential candidates for association with SPTB in a population of preterm singleton infants (n = 406) and their mothers (n = 308), and in mothers with term deliveries (n = 201) and their infants (n = 201), all originating from northern Finland.