Peripheral CD4+CD25+FOXP3+Tregs Cell Distribution in Women With and Without a History of Recurrent Pregnancy Loss in Relation to ACE rs4646994 (I/D) Polymorphism

PROBLEM: Recurrent pregnancy loss (RPL) a reproductive concern affects 1%-5% of couples worldwide and 50% of the cases are idiopathic. Pregnancy, a dynamic state of inflammation is influenced by diverse physiological factors. A multifunctional angiotensin converting enzyme (ACE) has direct effect on inflammation, oxidative stress, and fibrinolytic balance through Angiotensin-II. By blocking the NF-κB1 transcription factor complex, ACE inhibitors stimulate regulatory T-cells (Tregs). Based on this, we postulated that ACE functional polymorphism(s) may influence the Tregs in RPL. AIM: To assess the association of rs4646994 (I/D) polymorphism with circulating Tregs in south Indian pregnant women with (RPL) and without (nRPL) the history of RPL. METHODS OF STUDY: Genomic DNA and peripheral blood mononuclear cells (PBMC's) from nRPL(60) and RPL(77) pregnant women were isolated and subjected to PCR for rs4646994 genotyping and flow cytometry for enumeration of Tregs, respectively. RESULTS: We observed significantly diminished circulating Tregs (p < 0.0001) in RPL over the nRPL and lack of association of rs4646994 polymorphism with RPL. However, consistently lower Tregs irrespective of the genotypes within RPL group (p > 0.05) and significant elevation in percentage of Tregs in nRPL pregnant women with II (p = 0.003) and ID (0.007) genotypes when compared to their respective counterparts in RPL group was noted. CONCLUSION: This is first study to explore the association between ACE genotypes and distribution of Tregs in RPL. Understanding the relation may help resolve to certain extent the heterogeneity existing in idiopathic RPL for the better management. The limitation of the study is small sample size and lack of information on serum ACE levels.