Maternal FNDC5 and ADIPOQ Genetic Variants as Potential Modulators of Susceptibility to Spontaneous Preterm Birth

Preterm birth (PTB) is a complex and heterogeneous pregnancy outcome in which maternal metabolic and endocrine pathways may contribute to susceptibility to preterm delivery. This study investigated whether two maternal genetic variants involved in metabolic signaling, ADIPOQ rs266729 and FNDC5 rs1746661, are associated with preterm birth (PTB) in a Croatian population. This case–control study included 401 women: 200 with PTB and 201 with term delivery. Maternal genomic DNA was isolated from peripheral blood, and both variants were genotyped using TaqMan-based real-time PCR. Genotype and allele distributions, inheritance models, allelic combinations, logistic regression, and gene–gene interaction were analyzed. Neither variant was significantly associated with overall PTB, and no significant gene–gene interaction was observed (p = 0.18). In early PTB, only a borderline, non-significant tendency toward a higher ADIPOQ rs266729 G allele frequency was found (39% vs. 27%; OR 1.74, 95% CI 0.99–3.04; p = 0.05), which was not supported by genotype, inheritance-model, or regression analyses. The G–T allelic combination was more frequent in early PTB (13.6% vs. 4.6%; p = 0.03) but not after Benjamini–Hochberg correction (adjusted p = 0.09). No significant association between the investigated variants and PTB was demonstrated. The borderline findings in early PTB are hypothesis-generating and require replication in larger cohorts.