Feb. 8, 2010 In a study to be presented February 4 at the Society for Maternal-Fetal Medicine's (SMFM) annual meeting, The Pregnancy Meeting ™, in Chicago, researchers will show the use of haplotype tagging (hap-tag) single-nucleotide polymorphisms (SNPs) 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 (SPTD). The new study sought to determine if an environmental exposure associated with maternal inflammation, bacterial vaginosis (BV), 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 hap-tag SNPs in 5 BioCarta and KEGG pathways in which >3 SNPs were strongly associated (P<0.01) with SPTD at <37 weeks (Illumina GoldenGate 1,536-SNP custom chip panel). Associations between genotype distributions and SPTD were examined using Fisher's exact tests.
In the cohort, 68 women experienced SPTD at <37 wk, while 676 women delivered at term (9.1% SPTD rate). 306 women had asymptomatic BV (Nugent score *7) at 26-28 wk, and BV was not associated with an increased risk of SPTD (P=0.30). 20 hap-tag SNPs were associated with an increased risk of SPTD (P<0.05) in the BV+ group. For 9 SNPs in 3 genes (FLT1, PRKCA, and IL6), the OR of SPTD ranged from 2.0-7.0 among BV+ women who were carriers of the rare allele, and the OR for SPTD were 2.0-5.0 times greater among BV+ women than among BV- women (P<0.05 for test of homogeneity between ORs).
"The result is that chip assays for hap-tag SNPs provide a powerful tool for studying genes related to preterm birth and increase our potential to find groups of SNPs 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 SNP is related with a large percentage of preterm births."
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