P-90: Maternal Susceptibility to Pre-Eclampsia in South Indian Women: FOXP3 Gene

Background: Pre-eclampsia is a multifactorial pregnancy specific vascular disorder characterized by hypertension and proteinuria. It affects around 3-5% pregnancies worldwide. The aetiology and pathophysiology of PE remain poorly understood. But it is generally accepted defective placentation during the early stage of pregnancy most likely in combination with maternal and environmental factors could lead to systemic inflammation, endothelial dysfunction and the manifestation of the clinical symptoms. Regulatory T (Treg) cells accumulate in the decidua and are elevated in maternal blood early in the first trimester in normal pregnancy. FOXP3 gene is a master control gene for the development and natural function of Treg cells, plays an important role in the maintenance of self-tolerance and physiological immune responses. It is also suggested to mediate maternal tolerance to the fetus. Inadequate number of Treg cells or their functional deficiency are linked with infertility, miscarriage and pre-eclampsia. Alterations in genes controlling these processes may impart susceptible/protective genotypes that may increase/decrease the risk for pre-eclampsia. The present study deals with -3279 A>C polymorphism in the promoter region and a deletion in exon-2 within the FOXP3 gene in pre-eclamptic and normal pregnant women in order to assess the maternal susceptibility to preeclampsia. Materials and Methods: A total of 497 subjects viz. 282 PE patients and 215 normal pregnant women as controls of South Indian origin were recruited from Gandhi and J.J. hospitals, Hyderabad, India. Institutional ethical clearance and informed consent was obtained. Genomic DNA was isolated from the blood samples using standard protocol and genotyping was done for promoter -3279 A>C polymorphism applying the PCR-SSP and exon-2 deletion by PCR-RFLP. Results: Findings of study showed 27.65% vs 54.4%, of AA genotype, 47.51% vs 36.74% AC heterozygotes and 24.82% vs 8.83% CC homozygotes in PE patients compared to controls respectively for FOXP3 promoter -3279 A > C polymorphism. C allele frequency was observed to be higher in patients than in controls (49% vs 27%). When the three individual genotypes were compared with others the following observations were made (i) CC vs others OR = 3.4062 (p<0.0001) (ii) AA vs others OR = 2, (p<0.0001) (iii) AC vs others, OR =1.56 (p<0.01). None of the 215 controls showed deletion mutation in exon-2 of FOXP3. However, 1.06% of the patients exhibited this mutation in heterozygous condition and no homozygotes were observed. Conclusion: Our results are suggestive of significant involvement of FoxP3 gene promoter SNP and deletion mutation of exon -2 in the aetiopathogenesis of PE in South Indian women.