TNF-α and MTHFR Polymorphisms Associated with Cerebral Palsy in Chinese Infants

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Cerebral palsy (CP) pathogenesis is complex, with genetic and environmental factors implicated.
• Tumor Necrosis Factor-alpha (TNF-α) and Methylenetetrahydrofolate Reductase (MTHFR) genes are crucial in inflammatory and metabolic pathways potentially relevant to CP.

Purpose of the Study:

• To investigate the association between specific polymorphisms in TNF-α (rs361525, rs1799724) and MTHFR (rs1476413, rs9651118) genes and the risk of cerebral palsy in Chinese infants.
• To explore the potential interaction effects of these polymorphisms on CP development.

Main Methods:

• Genotyping of 105 CP patients and 114 healthy controls for selected TNF-α and MTHFR polymorphisms using TaqMan allelic discrimination assay.
• Statistical analysis including Odds Ratios (OR) and 95% Confidence Intervals (CI) to assess the strength of associations.
• Subgroup analysis based on gestational age and measurement of TNF-α protein concentrations.

Main Results:

• Significant differences in allele distributions for TNF-α rs1799724 and both allele and genotype distributions for MTHFR rs9651118 between CP cases and controls.
• Significant associations found between TNF-α rs361525 and MTHFR rs9651118 polymorphisms and CP, particularly in subgroups based on gestational age.
• Elevated TNF-α protein levels in patients with the rs361525 GG genotype and a significantly increased risk of CP associated with the interaction of TNF-α rs1799724 and MTHFR rs9651118.

Conclusions:

• Polymorphisms in TNF-α and MTHFR genes are potentially involved in the pathogenesis of cerebral palsy in Chinese infants.
• The interaction between specific TNF-α and MTHFR polymorphisms may contribute to an increased risk of CP.
• These findings highlight the role of genetic factors in CP etiology and suggest potential targets for future research.