Evidence of a gene-environment interaction that predisposes to spontaneous preterm birth: a role for asymptomatic bacterial vaginosis and DNA variants in genes that control the inflammatory response.
OBJECTIVE
We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susceptibilities for spontaneous preterm delivery within genes that regulate the inflammatory response.


METHODS
Maternal DNA samples and vaginal smears for Gram staining were collected from 743 women (68 preterm births). We used a 1536-single nucleotide polymorphism (SNP) custom chip to study associations between genotype distributions and preterm birth.


RESULTS
For 8 SNPs in 3 genes (protein kinase C alpha, fms-like tyrosine kinase 1, and interleukin 6), the odds ratios for preterm birth ranged from 1.9-4.0 among women with susceptible genotypes who were BV positive. The odds ratios for preterm birth were 2.0-5.0 times greater among women who were BV positive than among women who were BV negative. The significance of these differences was demonstrated by logistic regression analyses for genotype/BV interaction.


CONCLUSIONS
These results demonstrate that the risk of preterm delivery that is associated with tag SNPs in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis.
Gómez
Luis M
LM
Division of Maternal-Fetal Medicine, Maternal and Child Research Program, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Sammel
Mary D
MD
Appleby
Dina H
DH
Elovitz
Michal A
MA
Baldwin
Don A
DA
Jeffcoat
Marjorie K
MK
Macones
George A
GA
Parry
Samuel
S
D000293:Adolescent; D000328:Adult; D004777:Environment; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000235:genetics*; D016015:Logistic Models; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D051571:Protein Kinase C-alpha / Q000235:genetics*; D012307:Risk Factors; D014626:Vaginal Smears; D016585:Vaginosis, Bacterial / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D055815:Young Adult
C508600:IL6 protein, human; D015850:Interleukin-6; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D051571:Protein Kinase C-alpha