Preterm birth and genitourinary tract infections: assessing gene-environment interaction

Area of Science:

• Genetics
• Obstetrics
• Infectious Diseases

Background:

• Preterm birth (PTB) is a leading global cause of perinatal mortality.
• The etiology of PTB is complex, involving genetic and environmental factors.
• Understanding gene-environment interactions is crucial for PTB prevention.

Purpose of the Study:

• To investigate the statistical interaction between genes and vaginal-urinary tract infections (VI-UTI) in relation to PTB risk.
• To analyze these interactions across different clinical subtypes of PTB.
• To identify specific genetic variants and infection types contributing to PTB risk.

Main Methods:

• Genotyping of 24 single nucleotide polymorphisms (SNPs) in 18 candidate genes.
• Analysis of 352 fetal triads and 106 maternal triads.
• Conditional logistic regression and genotypic transmission/disequilibrium tests to evaluate statistical interactions.

Main Results:

• Specific fetal SNPs (e.g., rs11686474, rs4458044, rs883319, rs2277698, rs5742612) and maternal SNPs (e.g., rs1882435, rs4458044) were associated with increased PTB risk.
• Interactions varied by infection type (UTI vs. VI), maternal/fetal genotype, and PTB clinical subtype (idiopathic, PPROM, spontaneous).
• Notable associations were found in PTB-idiopathic, PPROM, and spontaneous PTB subtypes.

Conclusions:

• Maternal and fetal genes involved in inflammatory/infectious and hormonal regulation processes interact with VI-UTI to increase PTB risk.
• These gene-infection interactions are specific to PTB clinical subtypes and infection types.
• Findings contribute to understanding PTB etiology and may inform prevention strategies.