Potential role of a single nucleotide polymorphism in the gelatinase A promoter as a risk factor for premature birth

Background: Gelatinase A (matrix metalloproteinase-2) is an important enzyme in many biologic processes. Prevailing data reveal a functional polymorphism at bp -1575 in the human gelatinase A promoter, which is associated with diminished transcriptional response to estrogen and genetic fitness. The reason for the disequilibrium of the -1575AA genotype within the Hardy-Weinberg distribution remains unknown. We therefore screened full-term and premature newborns to investigate whether the -1575AA genotype might increase the risk of premature delivery, which is often associated with decreased survival of infants. Methods: DNA from 959 full-term and 358 premature newborns of North German Caucasian origin was amplified from dried blood on filter paper used for standard newborn screening in Germany. Genotypes were defined by restriction digest of PCR products. Results: No statistically significant difference in Hardy-Weinberg distribution was discovered between fullterm and premature infants. However, a trend towards the expected number of homozygous mutants was seen in premature females. Conclusions: Our results warrant the hypothesis that the disequilibrium in -1575AA mutational variant might be due to early abortions; the reduced responsiveness to estrogen stimulation in this genotype might be responsible for inadequate estrogen-stimulated gelatinase A enhancement during trophoblast invasion and uterine implantation of the embryo. Further genotyping of couples seeking help from fertility clinics might help to answer this question.