R147W in PROC Gene Is a Risk Factor of Thromboembolism in Thai Children

Sirachainan, Nongnuch; Chuansumrit, Ampaiwan; Sasanakul, Werasak; Yudhasompop, Najwa; Mahaklan, Lalita; Vaewpanich, Jarin; Charoenkwan, Pimlak; Kanjanapongkul, Somjai; Visudtibhan, Anannit; Wongwerawattanakoon, Pakawan

doi:10.1177/1076029617709085

Cited by 9 publications

(10 citation statements)

References 20 publications

(36 reference statements)

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“…This may be explained by the different genetic background for VTE between Caucasian and East Asian populations [21,30]. Protein S deficiency and protein C deficiency are more common in the Thais [31,32], but the weaker thrombophilia mutations are common in Caucasians [17,18]. Our study suggests that thrombophilia workups are potentially helpful for the recurrent risk stratification in Thai VTE patients without cancer.…”

Section: Discussionmentioning

confidence: 83%

Risk factors for venous thromboembolism (VTE) recurrences in Thai patients without cancer

Satpanich

Rojnuckarin

2018

Hematology

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Introduction: Studies in Western countries show that VTE recurrent rates are lower in the presence of a transient provoking factor, older age, female sex and/or hormonal use, while thrombophilia (factor V Leiden or prothrombin mutation) has no predictive role. This study aimed to determine the incidence and risk factors of recurrent VTE in Asian patients. Method: This is a retrospective cohort study in adult VTE patients who were diagnosed during 2004-2014, had no active cancer and followed-up for at least 1 year. Results: There were 198 patients. The mean age was 58.2 ± 17.6 years and 68.2% were female. The diagnoses were deep vein thrombosis (56%), pulmonary embolism (32%) or both (12%). They were provoked by major surgery in 21.7%. Thrombophilia (antiphospholipid syndrome or protein C or protein S deficiency) was found in 11.6%. The recurrent rate during the median follow-up time of 52 months was 2.2 (95% confidence interval [CI] 1.46-3.31) per 100 patient-years. Presence of thrombophilia was independently associated with recurrences with the adjusted hazard ratio (aHR) of 3.52 (95% CI 1.32-9.42, p = 0.01). There were 144 patients who discontinued anticoagulants. During the median time of 55 months after stopping anticoagulants, the recurrent rate was 4.3 per 100 patient-years. Thrombophilia was associated with recurrences with aHR of 4.00 (95% CI 1.42-11.31, p = 0.01), while male sex, younger age, provoking conditions and hormone use showed no significant association. Conclusion: VTE recurrent rate in Asians is comparable to Caucasians, but thrombophilia is the strongest risk factor.

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Section: Discussionmentioning

confidence: 83%

Risk factors for venous thromboembolism (VTE) recurrences in Thai patients without cancer

Satpanich

Rojnuckarin

2018

Hematology

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“…This suggests that the PC p.Arg189Trp variant is a highly frequent thrombophilia among Chinese and Malay, and possibly among Batak and Myanmar. Recently, this variant was reported to be prevalent in the general Thai population (allele frequency, 3.0%) and was identified as a risk factor for thromboembolism in subjects <18 years old 17 …”

Section: Resultsmentioning

confidence: 99%

Racial differences in protein S Tokushima and two protein C variants as genetic risk factors for venous thromboembolism

Tsuda

Noguchi

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background Racial differences in genetic risk factors for venous thromboembolism (VTE) are elucidated, with factor V Leiden and prothrombin G20210A being prevalent among the Caucasian population but rare among non‐Caucasians. Objectives To assess the worldwide distribution of three gene polymorphisms previously identified as genetic risk factors among East Asian subpopulations: protein S (PS) Tokushima (p.Lys196Glu), protein C (PC) p.Arg189Trp, and PC p.Lys193del. Methods An international collaborative study group of seven centers in five countries—Japan, South Korea, Singapore, Hungary, and Brazil—was created, and genotype analyses were performed. A total of 2850 unrelated individuals (1061 patients with VTE and 1789 controls) were included. Results PS Tokushima was confined to Japanese patients with VTE (allele frequency, 2.35%) and controls (1.12%), with an odds ratio (OR) of 2.15 (95% confidence interval, 1.16‐3.99). PC p.Arg189Trp carriers were prevalent among Chinese and Malay patients with VTE in Singapore, with allele frequencies of 10.53% and 22.73%, respectively. Carriers of PC p.Lys193del were identified among Japanese and Korean patients with VTE (0.87% and 2.35%, respectively) and controls (0.36% and 1.07%, respectively), with the OR for VTE not being significant, and Chinese patients with VTE in Singapore (5.26%). In contrast, no carriers of PS Tokushima and two PC gene variants were found among patients with VTE or controls from Hungary, Brazil, or Indians in Singapore. Conclusion The three variants were prevalent among East and Southeast Asians, having some differences in geographic distribution, but were absent among Caucasian subpopulations and Brazilians.

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“…The strength of our study was the relatively large number of pediatric patients with both VTE and ATE, as PC deficiency can also cause ATE in pediatric populations. 7 Also, the ethnicity effects on the SNPs distribution in Thais had never been reported.…”

Section: Discussionmentioning

confidence: 99%

“…6 Transcription starts at exon 1 while translation starts at exon 2. 6 The most common mutation of PROC gene among Thai and Taiwanese Chinese populations is R147W 7 or R189W, according to Human Genome Variation Society. In Caucasians, there are 4 common mutations of PROC : R230C, Q132stop, R306stop, and 3363insC.…”

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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R147W in PROC Gene Is a Risk Factor of Thromboembolism in Thai Children

Cited by 9 publications

References 20 publications

Risk factors for venous thromboembolism (VTE) recurrences in Thai patients without cancer

Risk factors for venous thromboembolism (VTE) recurrences in Thai patients without cancer

Racial differences in protein S Tokushima and two protein C variants as genetic risk factors for venous thromboembolism

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

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