Understanding the potential immunogenetic role of TNFα-308 polymorphism in the pathogenesis of recurrent miscarriage

Abstract

BackgroundRecurrent miscarriage (RM) represents the spontaneous termination of two or more successive pregnancies. TNFα is a proinflammatory cytokine that is often considered harmful for embryonic development when expressed beyond normal levels. AimThe study was conducted to assess the association between TNFα-308 polymorphism and RM pathogenesis. MethodsSamples of blood were obtained from patients and controls through venipuncture. The levels of TNFα in serum were measured by ELISA. TNFα gene promoter-associated single-nucleotide polymorphism was investigated with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques with precise primers and the restriction endonuclease, NcoI. ResultsSerum TNFα levels in patients were considerably high (p < 0.05) than controls. The genotype and allele frequencies for TNFα gene polymorphism differs significantly (p = 0.0089; p = 0.0043 respectively) between patients and controls. The TNFα-308 SNP exhibited a link with higher RM risk in heterozygous (GG vs. GA; OR: 3.086, 95% CI: 1.475–6.480; p: 0.0027), dominant (GG vs. GA + AA; OR: 2.919, 95% CI: 1.410–6.056, p: 0.0038), and allelic/codominant (G vs. A; OR: 2.449, 95% CI: 1.313–4.644, p: 0.0064) models. However, this SNP showed an insignificant association with higher and lower RM risk in homozygous (GG vs. AA; OR: 1.915, 95% CI: 0.3804–10.99, p: 0.6560) and recessive (AA vs. GA + GG; OR: 0.6596, 95% CI: 0.1152–3.297, p: >0.9999) models, respectively. Further, the TNFα-308G/A genotype frequencies were in concord with HWE both in the controls (χ2 = 3.235; p = 0.1985) and the patients (χ2 = 0.0117; p = 0.9942). ConclusionThe serum TNFα levels were significantly higher in the patients than the controls. The genotyping analysis also demonstrated that TNFα-308G/A SNP significantly increases the overall risk of RM, suggesting that the SNP modulates the TNFα gene expression and thereby increases serum TNFα levels that adversely affect the pregnancy outcome.