The Importance of Gene Variants Related to Folate Uptake and Distribution in the Etiology of Recurrent Miscarriage and Intrauterine Fetal Demise

(1) Background: The study involves an assessment of the frequency of selected gene variants related to folate uptake and distribution (FOLR1 rs2071010, rs630074, FOLH1 rs61886492, GGH rs11545078, rs3758149 and SLC19A1 rs1051266) in a group of women with fetal demise in the Polish population. (2) Methods: A total of 310 subjects were enrolled in the study. There were 110 females with idiopathic recurrent miscarriages (RM), 80 with stillbirth (IUFD) and 120 healthy controls. Designated SNVs were determined by using PCR-RFLP methods. The difference in fetal demise prevalence was assessed using a chi-square test and logistic regression analysis. (3) Results: The rs630074 variant of the FOLR1 gene is associated with a statistically significant increase in the risk of IUFD in a recessive model (OR = 2.03, 95%CI: 1.06–3.90, p = 0.033). The rs61886492variant f FOLH1 is linked to an increased risk of IUFD in co-dominant (p = 0.030), dominant (OR = 2.62, 95%CI: 1.07–6.38, p = 0.032) and log-additive models (OR = 2.64, 95%CI: 1.15–6.06 p = 0.030). In female carriers of the A allele, the risk of IUFD was 2.8 times higher compared to the control group. No relationship between the mother’s genotype and the newborn’s birth weight or placental weight was observed for the studied SNVs. (4) Conclusions: Our study finds that the rs61886492 variant of the FOLH1 gene is associated with IUFD in Polish women. However, pregnancy failures have a multifactorial pathology and other genetic or environmental factors may also contribute to their complex etiology. Further research, preferably with larger groups of women from different ethnic backgrounds, is needed to confirm the results of the current study.