Correlation of MTHFR (methylenetetrahydrofolate reductase) gen polymorphism, folate and neonatal hyperbilirubinemia.

Objective. Investigate the distribution of methylenetetrahydrofolate reductase (MTHFR) genotypes in newborns with hyperbilirubinemia and explore their correlation with folate concentration and bilirubin elevation. Methods. Neonates with hyperbilirubinemia were categorized into mild, moderate, and severe elevation groups based on total bilirubin levels. MTHFR C677T genotype (CC wild-type, CT heterozygous mutant, TT homozygous mutant) was detected using PCR fluorescent probe and folate by chemiluminescence assay. Chi-square tests, ANOVA, and ordered logistic regression were used for analysis. Results. A total of 132 neonates were included. The moderate and severe elevation groups predominantly exhibited the CT genotype (54.9% and 58.8%), while the mild elevation group predominantly showed the CC genotype (43.3%). The mutant (CT+TT) proportions in the moderate and severe groups were 76.5% and 90.2%, respectively, greater than the 67.1% reported in a large-scale Chinese investigation. Genotype (χ² = 13.665, P = 0.008) and allele (χ² = 6.081, P = 0.048) distributions differed significantly among groups. Folate levels were significantly lower in the mutant genotype than in the wild-type (t = 2.162, P = 0.032). Ordered logistic regression analysis indicated a negative correlation between folate levels and the degree of hyperbilirubinemia (P ≤0.001). TT (95% CI: 1.012-1.974, P = 0.042) and CT (95% CI: 1.069-1.823, P = 0.014) genotypes were identified as risk factors for elevated bilirubin. Conclusion. MTHFR C677T polymorphism and serum folate levels are associated with the severity of neonatal hyperbilirubinemia. MTHFR C677T mutation may exacerbate bilirubin metabolism disorders by inhibiting folate metabolism and promoting homocysteine accumulation, offering potential references for disease risk assessment.