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. 2022 Oct;20(10):2419-2428.
doi: 10.1111/jth.15814. Epub 2022 Jul 31.

Platelet protease activated receptor 4 (PAR 4) receptor genotype is associated with an increased risk of preterm birth

Rupsa C Boelig  1   2 , Tara J Cahanap  1 , Lin Ma  3 , Tingting Zhan  4 , Vincenzo Berghella  1 , Joanna S Y Chan  5 , Walter K Kraft  2 , Steven E Mckenzie  3
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Free article

Platelet protease activated receptor 4 (PAR 4) receptor genotype is associated with an increased risk of preterm birth

Rupsa C Boelig et al. J Thromb Haemost. 2022 Oct.
Free article

Abstract

Background: Platelet protease activated receptor-4 (PAR4) Thr120 is a common genetic variant associated with increased platelet activity. Increased platelet activity is implicated in the pathogenesis of preeclampsia and preterm birth.

Objective: Compare the rate of preeclampsia and preterm birth in pregnant individuals homozygous for PAR4 Thr120 variant vs not.

Study design: This is a prospective cohort study of patients who delivered November 2020-July 2021. Maternal blood collected on admission for PAR4 genotyping. The primary outcome was the rate of preeclampsia/gestational hypertension in those with Thr/Thr genotype compared with Ala/Thr or Ala/Ala. Secondary outcomes included rates of preterm birth and placental pathology.

Results: Three hundred and twenty singletons were included and 52 (16.3%) were PAR4 Thr/Thr. Those PAR4 Thr/Thr were more likely to be Black (67.3% vs 29.5%, p < .001), younger (28 ± 6 vs 31 ± 6, p = .004), and have higher body mass index (35.2 ± 6.8 vs 33.1 ± 7.4, p = .047). There was no difference in preeclampsia/gestational hypertension (19.2% vs 22.8%, p = .705). Those Thr/Thr had a significantly higher rate of preterm birth (15.4% vs 3.7%, adjusted odds ratio [aOR] 4.04 [1.47-11.10], p = .007), indicated preterm birth because of fetal growth restriction or preeclampsia (5.8% vs 0.4%, aOR 10.03 [1.48-67.87], p = .02), spontaneous preterm birth (7.7% vs 2.2%, aOR 4.81 [1.27-18.27], p = .02), and placental intervillous thrombosis (18.5% vs 7.9%, aOR 4.12 [1.14-14.92], p = .03).

Conclusion: Platelet receptor PAR4 Thr120 is a common variant associated with an increased risk of placental vascular pathology and preterm birth in homozygous individuals. Although a cohort study cannot establish causation, this strong association warrants further exploration.

Keywords: PAR4; genetics; platelet; preeclampsia; preterm birth; protease activated receptor 4.

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References

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