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Association of Trefoil Factor 3 Gene Polymorphisms with Recurrent Spontaneous Abortion in a North Indian Population:
Monica Agrawal1, Nitu Nigam2, Sangeeta Goel3
1Department of Obstetrics and Gynaecology King George's Medical University, Lucknow, Uttar Pradesh, India.
Background:
Recurrent spontaneous abortion (RSA) is a multifactorial reproductive disorder affecting 1%-2% of couples globally, with up to 50% of cases remaining idiopathic. Trefoil factor 3 (TFF3), a mucosal protective peptide expressed in the endometrium during the implantation window, supports epithelial repair and mucus production essential for successful pregnancy. Genetic variants in TFF3 have been implicated in idiopathic RSA in some populations, but data from Indian cohorts are lacking.
Aim:
The aim is to evaluate the prevalence of RSA in a North Indian population and investigate associations between TFF3 gene polymorphisms (rs225439 G/A and rs7743614 G/C) and RSA risk, adjusting for maternal age.
Materials And Methods:
This case-control study included 50 women with RSA (≥2 consecutive spontaneous abortions, 5-21 weeks of gestation) and 50 age-matched healthy controls recruited from Queen Mary's Hospital, Department of Obstetrics and Gynaecology , King George's Medical University, Lucknow. Genomic DNA was extracted from peripheral blood and genotyped for rs225439 and rs7743614 using TaqMan assays, with results validated by Sanger sequencing. Genotype distributions were tested for Hardy-Weinberg equilibrium. Associations were assessed using Chi-square tests, unadjusted odds ratios (OR), and age-adjusted logistic regression. Statistical analysis was performed with SPSS v23 (P < 0.05 significant).
Results:
Mean age was comparable between cases (28.80 ± 4.55 years) and controls (27.84 ± 4.06 years; P = 0.268), while mean abortions were significantly higher in cases (2.74 ± 0.80 vs. 1.92 ± 0.72; P < 0.001). Genotype frequencies for rs225439 (GG/GA/AA) and rs7743614 (GG/GC/CC) did not differ significantly between groups (all P > 0.05). Univariate ORs were nonsignificant; the highest adjusted OR was for rs225439 GA (OR = 5.64, 95% confidence interval: 0.63-50.70; P = 0.123). Age-adjusted logistic regression confirmed no significant association for either single nucleotide polymorphism or age (all P > 0.05).
Conclusion:
No significant association was found between TFF3 polymorphisms rs225439 and rs7743614 and RSA in this North Indian cohort. Larger, multi-centric studies with haplotype analysis and functional validation are needed to clarify the role of TFF3 in idiopathic RSA.
