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Impact of Tissue Factor Pathway Inhibitor Gene Polymorphisms (33T/C and 264V/M) on Plasma TFPI Levels and their Influence on Risk of Recurrent Pregnancy Loss in India

K. Kishor1, A. Sharma1, S. Maharana2, R. Ranjan1, R. Kumar1, S. Tyagi1, R. Saxena3, M. Mahapatra1

1All India Institute of Medical Sciences, New Delhi, India, 2Central University of Tamil Nadu, Thiruvarur, India, 3Medanta, the Medcity, Gurugram, India

Abstract Number: PB1302

Meeting: ISTH 2021 Congress

Theme: Women Health » Pregnancy and Pregnancy Complications

Background: Recurrent pregnancy loss (RPL) is a complex, multifactorial disease, with a frequency of 0.5–3% in all couples trying to conceive. Etiology of approximately 40–50% of all RPL remain unexplained.  Low TFPI level increased the risk of RPL in the West. However, association of TFPI levels with its polymorphisms and their role in Indian RPL patients is not yet studied.

Aims: To find out the distribution of TFPI 33T/C and 264V/M polymorphisms, their effects on TFPI levels and risk of RPL in India.

Methods: RPL patients with at least 3 consecutive pregnancy losses before 20 weeks of gestational age and equal number of healthy women with, at least one naturally conceived pregnancy studied. Plasma TFPI levels were determined by ELISA and its normal range determined (Mean±2SD of TFPI levels in controls). TFPI polymorphisms, 33T/C and 264V/M were detected by PCR-RFLP.

Results: 80 RPL patients, median age 33 years range (21-44 years) were recruited. Mean TFPI level was significantly lower in patients (37.32±13.92 ng/ml) than controls (48.15±13.35 ng/ml, p=0.001). Moreover, 11 patients  had low TFPI (<21.45 ng/ml), whereas no control had low TFPI. CT and TT genotypes of 33T/C polymorphism was significantly lower 31 (38.75%) in patients than 44 (55%) controls (p=0.039). The distribution of heterozygous genotype (VM) of 264V/M polymorphism was similar 5 (6.25%) in patients and 3 (3.75%) controls (p=0.719) however, no homozygous mutant genotype (MM) was observed in study subjects. Relation between the TFPI levels and their genotypes and relative risk of RPL are shown in table.

TFPI polymorphisms TFPI Levels ng/ml
(Mean±SD)
OR (95% CI) ORA (95% CI)
33T/C           TT
                     TC
                     CC
34.02±11.51
45.60±11.72
70.96± 13.78
0.001*, 0.001$, 0.001# 
1.0
0.536(0.279-0.927)
0.327(0.112-1.062)
1.0
0.441(0.22-0.85)
0.202(0.07-0.822)
264V/M         VV
                     VM
                     MM
48.46±13.76
42.88±12.65
……….
0.491*, 0.492$ 
1.0
2.260(0.609-9.78)
–
1.0
2.85(0.91-13.07)
–
P-value <0.05 is statistically significant: *Overall p value, # Wild Vs Heterozygous, $Wild Vs Homozygous, ORA: adjusted for BMI, DM-Type-II, hypertension.

TFPI levels according to genotypes of TFPI polymorphisms and relative risk of RPL

Conclusions: As in the West, low TFPI level predisposes to RPL. 33T/C polymorphism associated with high plasma TFPI level and has a protective role against RPL. 264V/M polymorphism neither associated with TFPI level nor with risk of RPL. A study with large sample size is required to confirm these findings.

To cite this abstract in AMA style:

Kishor K, Sharma A, Maharana S, Ranjan R, Kumar R, Tyagi S, Saxena R, Mahapatra M. Impact of Tissue Factor Pathway Inhibitor Gene Polymorphisms (33T/C and 264V/M) on Plasma TFPI Levels and their Influence on Risk of Recurrent Pregnancy Loss in India [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/impact-of-tissue-factor-pathway-inhibitor-gene-polymorphisms-33t-c-and-264v-m-on-plasma-tfpi-levels-and-their-influence-on-risk-of-recurrent-pregnancy-loss-in-india/. Accessed August 19, 2022.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/impact-of-tissue-factor-pathway-inhibitor-gene-polymorphisms-33t-c-and-264v-m-on-plasma-tfpi-levels-and-their-influence-on-risk-of-recurrent-pregnancy-loss-in-india/

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