Protective Effect of EBF Transcription Factor 1 (EBF1) Polymorphism in Sporadic and Familial Spontaneous Preterm Birth: Insights from a Case-Control Study

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes <i>Astrotactin 1</i> (<i>ASTN1</i>), <i>EBF Transcription Factor 1</i> (<i>EBF1</i>), <i>Eukaryotic Elongation Factor</i>, <i>Selenocysteine-tRNA Specific</i> (<i>EEFSEC</i>), <i>Microtubule-Associated Serine/Threonine Kinase 1</i> (<i>MAST1</i>), and <i>Tumor Necrosis Factor Alpha</i> (<i>TNF-α</i>) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks' gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks' gestation), and 281 control women. The analysis of <i>ASTN1</i> rs146756455, <i>EBF1</i> rs2963463, <i>EBF1</i> rs2946169, <i>EEFSEC</i> rs201450565, <i>MAST1</i> rs188343966, and <i>TNF-α</i> rs1800629 SNPs was performed using TaqMan real-time PCR. <i>p</i>-values were Bonferroni-adjusted for multiple comparisons. <i>EBF1</i> SNP rs2963463 was significantly associated with sPTB (<i>p</i> adj = 0.03). Women carrying the CC genotype had a 3-4-times lower risk of sPTB (<i>p</i> adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (<i>p</i> adj < 0.0001). All other associations were based on unadjusted <i>p</i>-values. The minor T allele of <i>EBF1</i> SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (<i>p</i> = 0.045). Similarly, the CC genotype of <i>ASTN1</i> SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (<i>p</i> = 0.019). Finally, the <i>TNF-α</i> SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (<i>p</i> < 0.05). The <i>EBF1</i> SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, <i>EBF1</i> SNP rs2946169 and <i>ASTN1</i> SNP rs146756455, as well as <i>TNF-α</i> SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively.