CHICAGO, IL — In a study was presented at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting, in Chicago, researchers will show the use of haplotype tagging single-nucleotide polymorphisms to study the relationship between genetic predispositions, an environmental factor – bacterial vaginosis, and preterm birth.

Studies previously demonstrated that genetic variation within genes that regulate the maternal inflammatory response are associated with an increased risk of spontaneous preterm delivery. The new study sought to determine if an environmental exposure associated with maternal inflammation, bacterial vaginosis, modifies these genetic susceptibilities.

The March of Dimes notes that babies born before 37 completed weeks of pregnancy are called premature, and in the United States, about 12.8 percent of babies (more than half a million a year) are born prematurely.

The study that was conducted was a prospective cohort study in which maternal DNA samples were collected from 744 women, and demographics and outcomes data were recorded. Vaginal smears for Gram-staining were obtained from subjects at 26-28 wk gestation. It studied haplotype tagging single-nucleotide polymorphisms in 5 BioCarta and KEGG pathways in which >3 single-nucleotide polymorphisms were strongly associated (P<0.01) with spontaneous preterm delivery at <37 weeks (Illumina GoldenGate 1,536-single-nucleotide polymorphism custom chip panel). Associations between genotype distributions and spontaneous preterm delivery were examined using Fisher’s exact tests.

In the cohort, 68 women experienced spontaneous preterm delivery at <37 wk, while 676 women delivered at term (9.1% spontaneous preterm delivery rate). 306 women had asymptomatic bacterial vaginosis (Nugent score *7) at 26-28 wk, and bacterial vaginosis was not associated with an increased risk of spontaneous preterm delivery (P=0.30). 20 haplotype tagging single-nucleotide polymorphisms were associated with an increased risk of spontaneous preterm delivery (P<0.05) in the bacterial vaginosis+ group. For 9 single-nucleotide polymorphisms in 3 genes (FLT1, PRKCA, and IL6), the OR of spontaneous preterm delivery ranged from 2.0-7.0 among bacterial vaginosis+ women who were carriers of the rare allele, and the OR for spontaneous preterm delivery were 2.0-5.0 times greater among bacterial vaginosis+ women than among bacterial vaginosis- women (P<0.05 for test of homogeneity between ORs).

“The result is that chip assays for haplotype tagging single-nucleotide polymorphisms provide a powerful tool for studying genes related to preterm birth and increase our potential to find groups of single-nucleotide polymorphisms in biologically relevant pathways that might cause preterm birth,” said Dr. Samuel Parry, the study’s author of the University of Pennsylvania in Philadelphia. “It is unlikely that any single single-nucleotide polymorphism is related with a large percentage of preterm births.”

- MFP Wire Services
- 02-05-2010