The M358R variant of α 1 -proteinase inhibitor inhibits coagulation factor VIIa

Sheffield, William P.; Bhakta, Varsha

doi:10.1016/j.bbrc.2016.01.069

Cited by 4 publications

(1 citation statement)

References 30 publications

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“…AAT Pittsburgh has a Met382Arg substitution (legacy Met358Arg) at the reactive Met-Ser site of AAT, which enables the protein to act as a potent thrombin inhibitor. [8][9][10] Patients with AAT Pittsburgh exhibit bleeding tendency. Severe AATD has been reported in cases with venous thromboembolism (VTE).…”

Section: Introductionmentioning

confidence: 99%

Thrombotic risk determined by rare and common SERPINA1 variants in a population‐based cohort study

Manderstedt

Halldén

Lind‐Halldén

et al. 2022

Journal of Thrombosis and Haemostasis

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Background Severe alpha‐1‐antitrypsin deficiency (AATD), phenotype PiZZ, was associated with venous thromboembolism (VTE) in a case‐control study. Objectives This study aimed to determine the genetic variation in the SERPINA1 gene and a possible thrombotic risk of these variants in a population‐based cohort study. Patients/Methods The coding sequence of SERPINA1 was analyzed for the Z (rs28929474), S (rs17580), and other qualifying variants in 28,794 subjects without previous VTE (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer study (1991–1996). Individuals were followed from baseline until the first event of VTE, death, or 2018. Results Resequencing the coding sequence of SERPINA1 identified 84 variants in the total study population, 21 synonymous, 62 missense, and 1 loss‐of‐function variant. Kaplan‐Meier analysis showed that homozygosity for the Z allele increased the risk of VTE whereas heterozygosity showed no effect. The S (rs17580) variant was not associated with VTE. Thirty‐one rare variants were qualifying and included in collapsing analysis using the following selection criteria, loss of function, in frame deletion or non‐benign (PolyPhen‐2) missense variants with minor allele frequency (MAF) <0.1%. Combining the rare qualifying variants with the Z variant showed that carrying two alleles (ZZ or compound heterozygotes) showed increased risk. Cox regression analysis revealed an adjusted hazard ratio of 4.5 (95% confidence interval 2.0–10.0) for combinations of the Z variant and rare qualifying variants. One other variant (rs141620200; MAF = 0.002) showed an increased risk of VTE. Conclusions The SERPINA1 ZZ genotype and compound heterozygotes for severe AATD are rare but associated with VTE in a population‐based Swedish study.

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Section: Introductionmentioning

confidence: 99%

Thrombotic risk determined by rare and common SERPINA1 variants in a population‐based cohort study

Manderstedt

Halldén

Lind‐Halldén

et al. 2022

Journal of Thrombosis and Haemostasis

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Pharmacokinetic Analysis of Four Bioactive Iridoid and Secoiridoid Glycoside Components of Radix Gentianae Macrophyllae and Their Synergistic Excretion by HPLC-DAD Combined with Second-Order Calibration

Yang

Liu

et al. 2017

Nat. Prod. Bioprospect.

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An HPLC-DAD method combined with second-order calibration based on the alternating trilinear decomposition (ATLD) algorithm with the aid of region selection was developed to simultaneously and quantitatively characterize the synergistic relationships and cumulative excretion of the four bioactive ingredients of Radix Gentianae Macrophyllae in vivo. Although the analytes spectra substantially overlapped with that of the biological matrix, the overlapping profiles between analytes and co-eluting interferences can be successfully separated and accurately quantified by the ATLD method on the basis of the strength of region selection. The proposed approach not only determined the content change but also revealed the synergistic relationships and the cumulative excretion in vivo of the four ingredients in urine and feces samples collected at different excretion time intervals. In addition, several statistical parameters were employed to evaluate the accuracy and precision of the method. Quantitative results were confirmed by HPLC-mass spectrometry. Satisfactory results indicated that the proposed approach can be utilized to investigate the pharmacokinetics of Radix Gentianae Macrophyllae excretion in vivo.Graphical Abstract

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Genes in Families

Cook

2019

Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics

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The M358R variant of α 1 -proteinase inhibitor inhibits coagulation factor VIIa

Cited by 4 publications

References 30 publications

Thrombotic risk determined by rare and common SERPINA1 variants in a population‐based cohort study

Thrombotic risk determined by rare and common SERPINA1 variants in a population‐based cohort study

Pharmacokinetic Analysis of Four Bioactive Iridoid and Secoiridoid Glycoside Components of Radix Gentianae Macrophyllae and Their Synergistic Excretion by HPLC-DAD Combined with Second-Order Calibration

Genes in Families

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