Low Levels of Protein Z Are Associated With HELLP Syndrome and its Severity

Kaygusuz, Işık; Fıratlı-Tuğlular, Tulin; Toptaş, Tayfur; Uğurel, Vedat; Demir, Muzaffer

doi:10.1177/1076029609357738

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…126 One study found a correlation between lower PROZ levels and severity of HELLP syndrome (MIM: 614985), a complication of preeclampsia that stands for hemolysis, elevated liver enzymes, and low platelets and which occurs in 10-20% of preeclamptic pregnancies. 123,127 However, no study on PROZ or other clotting factors in preeclampsia has been successfully replicated, likely due to the extreme heterogeneity of the disease and the mix of populations studied.…”

Section: Discussionmentioning

confidence: 99%

Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes

Nieves-Colón¹,

Rivera²,

Sandoval³

et al. 2022

The American Journal of Human Genetics

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Section: Discussionmentioning

confidence: 99%

Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes

Nieves-Colón¹,

Rivera²,

Sandoval³

et al. 2022

The American Journal of Human Genetics

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“…In contrast, a larger cross-sectional study found lower median levels of PROZ in preeclampsia outcomes but not IUGR or fetal demise (Erez et al, 2007). One study found a correlation between lower PROZ levels and severity of HELLP syndrome (a complication of preeclampsia that stands for haemolysis, elevated liver enzymes, and low platelets), which occurs in 10-20% of preeclamptic pregnancies (Haram, et al, 2014, Kaygusuz et al, 2011). However, no study on PROZ or other clotting factors in preeclampsia has been successfully replicated, likely due to the extreme heterogeneity of the disease and the mix of populations studied.…”

Section: Discussionmentioning

confidence: 99%

Clotting factor genes are associated with preeclampsia in high altitude pregnant women in the Peruvian Andes

et al. 2021

Preprint

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Study question: What is the genetic basis of preeclampsia in Andean families residing at high altitudes? Summary answer: A top candidate region associated with preeclampsia containing clotting factor genes PROZ, F7 and F10 was found on chromosome 13 of the fetal genome in affected Andean families. What is known already: Preeclampsia, a multi-organ complication of pregnancy, is a leading cause of maternal morbidity and mortality worldwide. Diagnosed by the onset of maternal hypertension and proteinuria after 20 weeks of gestation, this disorder is a common cause of preterm delivery and affects approximately 5-7% of global pregnancies. The heterogeneity of preeclampsia has posed a challenge in understanding its etiology and molecular basis. However, risk for the condition is known to increase in high altitude regions such as the Peruvian Andes. Study design, size, duration: To investigate the genetic basis of preeclampsia in a high-altitude resident population, we characterized genetic diversity in a cohort of Andean families (N=883) from Puno, Peru, a high-altitude city above 3,500 meters. Our study collected DNA samples and medical records from case-control trios and duos between 2011-2016, thus allowing for measurement of maternal, paternal, and fetal genetic factors influencing preeclampsia risk. Participants/materials, setting, methods: We generated high-density genotype data for 439,314 positions across the genome, determined ancestry patterns and mapped associations between genetic variants and preeclampsia phenotype. We also conducted fine mapping of potential causal variants in a subset of family participants and tested ProZ protein levels in post- partum maternal and cord blood plasma by ELISA. Main results and the role of chance: A transmission disequilibrium test (TDT) revealed variants near genes of biological importance in pregnancy physiology for placental and blood vessel function. The most significant SNP in this cluster, rs5960 (p<6x10-6) is a synonymous variant in the clotting factor F10. Two other members of the coagulation cascade, F7 and PROZ, are also in the top associated region. However, we detected no difference of PROZ levels in maternal or umbilical cord plasma. Limitations, reasons for caution: Our genome-wide association analysis (GWAS) was limited by a small sample size and lack of functional follow up. Our ELISA was limited to post-natal blood sampling (only samples collected immediately after birth). But, despite a small sample size, our family based GWAS design permits identification of novel significant and suggestive associations with preeclampsia. Further longitudinal studies could analyze clotting factor levels and activity in other pregnant cohorts in Peru to assess the impact of thrombosis in preeclampsia risk among Andean highlanders. Wider implications of the findings: These findings support previous evidence suggesting that coagulation plays an important role in the pathology of preeclampsia and potentially underlies susceptibility to other pregnancy disorders exacerbated at high altitudes. This discovery of a novel association related to a functional pathway relevant to pregnancy biology in an understudied population of Native American origin demonstrates the increased power of family-based study design and underscores the importance of conducting genetic research in diverse populations.

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“…[37,38] Reduced PZ levels (<1 μg/mL) were linked with several pregnancy complications including fetal demise, preeclamsia, small-for-gestational age, intrauterine growth restriction, HELLP syndrome, and idiopathic recurrent miscarriage. [37][38][39][40][41] As is known, approximately 3% of the etiology of SSNHL is from the return of venous thromboembolism, which is obstructing the circulation in the labyrinthine artery. Inadequate and/or ineffective release of ZP/ZPI complex may also participate the pathophysiology of SSNHL, particularly in patients with idiopathic SSNHL.…”

Section: Discussionmentioning

confidence: 99%

Is there any relationship between sudden sensorineural hearing loss and protein Z plasma levels?

Acar¹

2016

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Bu çalışmada protein Z plazma düzeyleri ile ani işitme kaybı arasında ilişki değerlendirildi. Hastalar ve Yöntemler: Ani işitme kaybı olan 20 hasta (14 erkek, 6 kadın; ort. yaş 51.6±14.6 yıl; dağılım 23-75 yıl) ve herhangi bir işitme sorunu olmayan 30 sağlıklı birey (14 erkek, 16 kadın; ort. yaş 46.8±8.9 yıl; yaş aralığı 30-64 yıl) araştırmaya dahil edildi. Protein C, protein S ve protein Z plazma düzeyleri ölçüldü. Bulgular: Çalışma grupları arasında protein S ve protein C düzeyleri karşılaştırıldığında istatistiksel olarak anlamlı bir fark bulunmazken (p=0.78 ve p=0.44), kontrol grubuna göre ani işitme kaybı olan grupta protein Z plazma düzeylerinin önemli ölçüde düşük olduğu bulundu ve fark istatistiksel olarak anlamlıydı (p<0.001). Sonuç: Damarsal nedenler ani işitme kaybı etyolojisinde yer alabilir. Ani işitme kaybı olan hastalarda protein Z plazma düzeylerindeki değişim arteriyel tromboembolizm veya venöz tromboz ile ilişkili olabilir. Anahtar sözcükler: Etyoloji; protein Z; ani işitme kaybı; tromboembolizm. ABSTR ACT Objectives: This study aims to evaluate the relationship between sudden sensorineural hearing loss and protein Z plasma levels. Patients and Methods: Twenty patients with sudden sensorineural hearing loss (14 males; 6 females; mean age 51.6±14.6 years; range 23 to 75 years) and 30 healthy subjects without any hearing problems (14 males, 16 females; mean age 46.8±8.9 years; range 30 to 64 years) were investigated. Protein C, protein S, and protein Z plasma levels were measured. Results: When protein S and protein C levels were compared between the study groups, we did not find a statistically significant difference (p=0.78 and p=0.44), whereas, protein Z plasma levels were found to be considerably lower in the sudden sensorineural hearing loss group than in the control group, and the difference was statistically significant (p<0.001). Conclusion: Vascular causes may be involved in the etiology of sudden hearing loss. Changes in protein Z plasma levels might be associated with arterial thromboembolism or venous thrombosis in patients with sudden sensorineural hearing loss.

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Low Levels of Protein Z Are Associated With HELLP Syndrome and its Severity

Cited by 5 publications

References 38 publications

Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes

Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes

Clotting factor genes are associated with preeclampsia in high altitude pregnant women in the Peruvian Andes

Is there any relationship between sudden sensorineural hearing loss and protein Z plasma levels?

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