A common polymorphism in the 5’ region of the human protein c gene binds USF1

Thain, Katherine R.; Nakada, Taka‐aki; Boyd, John H.; Russell, James A.; Walley, Keith R.

doi:10.1016/j.thromres.2012.02.045

Cited by 3 publications

(5 citation statements)

References 39 publications

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“…These results from the control group confirm that the PC levels in healthy individuals are determined by genetic variations. As mentioned in other studies , the higher CGTC haplotype frequency in the patients in the present study ( P = 0.005) demonstrated the influence on the thrombotic risk. This association was proven by the higher number of thrombotic episodes experienced by patients homozygous for the CGTC haplotype; conversely, patients homozygous for the TAAT haplotype had the lowest incidence of such events, supporting the notion of a protective effect as suggested previously by other authors .…”

Section: Discussionsupporting

confidence: 85%

“…The SNPs within the 5′ region of PROC , which causally contribute to down transcriptional regulation, show a correlation with low plasma levels of PC and are associated with adverse outcomes in a variety of clinical states. These SNPs, which extend from the promoter region to the end of intron 2, −1657C/T (rs1799808); −1644A/G (rs1799809); −1479A/T (rs1799810); and −141T/C (rs1158867), show a high degree of linkage disequilibrium (LD) . The CGT haplotype of −1657C/T, −1644 A/G, and −1479A/T is generally related to lower plasma PC levels than the complementary TAA haplotype and to a higher risk of thrombotic events.…”

mentioning

confidence: 99%

“…The transcriptional efficiency of PROC in these haplotypes has been described as driven by the SNPs at positions −1657 and −1644. The other two SNPs, −1479A/T and −141T/C, are in complete LD ( r 2 = 1) and may be involved in regulating splicing events with moderate thrombotic risk .…”

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confidence: 99%

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Familial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Study

Fidalgo

Martinho

Salvado

et al. 2015

European J of Haematology

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Introduction Inherited protein C (PC) deficiency is a well‐known risk factor for venous thrombosis (VT). Plasma PC levels are reliable in moderate to severe deficiencies; however, in mildly deficient individuals, the levels may overlap with those considered normal. Genetic studies of PROC, which encodes PC, could help identify carriers; genome‐wide association studies (GWAS) have shown that approximately 50% of phenotypic variation in PC deficiency is caused by the cumulative effects of mutations in several other loci, namely in the PROCR. Patients and methods With the main objective of determining the genotype/phenotype correlation in 59 Portuguese individuals from 26 unrelated families with history of thrombosis and repeatedly low/borderline PC plasma levels, we conducted a molecular study by direct sequencing of PROC; PROC promoter haplotypes and PROCR c.4600A>G polymorphism (rs867186), which are known to influence plasma PC concentrations, were also screened. Results Twelve different PROC mutations were identified, one of them not previously reported, p.Cys105Arg. The mutation types and locations as well as haplotype combinations correlated with the phenotypic severity. The most frequent mutation, p.Arg199X, correlated with the CGTC haplotype and was identified in nine families containing patients with higher numbers of VT episodes. This mutation in homozygous individuals for the CGTC haplotype is a significant risk factor for VT in Portuguese. Conclusion These genetic family studies allowed the identification of the unknown carriers and individuals at a higher thrombotic risk within each family, thus permitting the evaluation of the need for prophylactic measures, particularly in at‐risk situations.

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Section: Discussionsupporting

confidence: 85%

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confidence: 99%

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Familial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Study

Fidalgo

Martinho

Salvado

et al. 2015

European J of Haematology

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“… 11 Moreover, the 2 promoter SNPs (−1654C/T and −1641A/G) are in very high linkage disequilibrium with 2 SNPs in intron 2 (857 and 894) which have significant nuclear factors binding. 12 …”

Section: Introductionmentioning

confidence: 99%

“…11 Moreover, the 2 promoter SNPs (À1654C/T and À1641A/G) are in very high linkage disequilibrium with 2 SNPs in intron 2 (857 and 894) which have significant nuclear factors binding. 12 Three SNPs (À1654C/T, À1641A/G, and À1476A/T) have been identified in the promoter region of PROC. [13][14][15][16] Associations of these SNPs with PC levels and the risk of developing TE were found in many studies of adult populations.…”

Section: Introductionmentioning

confidence: 99%

PROC Promoter Single Nucleotide Polymorphisms Associated With Low Protein C Activity But Not Increased Risk of Thromboembolism in Pediatric Population

Udomkittivorakul

Sasanakul

Eu-ahsunthornwattana

et al. 2020

Clin Appl Thromb Hemost

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Protein C (PC) deficiency, caused by mutations of the PROC gene, is a common inherited risk factor of thromboembolism (TE) among Thai people. This study aimed to investigate the association of 3 single nucleotide polymorphisms (SNPs; −1654 C/T, −1641 A/G, −1461A/T) at the PROC promoter region with PC activity and the risk of developing TE. A total of 216 patient s with TE, diagnosed at aged 0 to 20 years, and 102 healthy adults were enrolled. The SNPs were identified by Sanger sequencing. Protein C activity was measured using an automated functional clotting assay. Linear and logistic regression analyses were used to determine the association of SNPs with PC activity and the risk of TE. Patients and controls with homozygous TAA (119.6% ± 26.1%) and CGT haplotypes (102.7% ± 22.6%) had significantly lower PC activity than those with a homozygous CAA haplotype (140.4% ± 44.9%); P = .027 and .016, respectively. However, none of these haplotypes increased the risk of TE. This study suggested that the 3 PROC promoter SNPs were shown to be associated with lower PC activity but did not increase the risk of TE.

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