Ponlapat Rojnuckarin1, Rung Settapiboon2, Benjaporn Akkawat2, Sudawadee Teocharoen2, Amornchai Suksusut2, Noppacharn Uaprasert2. 1. Research Collaborations in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Division of Hematology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Electronic address: Ponlapat.R@Chula.ac.th. 2. Research Collaborations in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Division of Hematology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Abstract
INTRODUCTION: In contrast to Caucasians, hereditary anticoagulant deficiencies are more common in Asians and mutations are heterogeneous among different countries. This study aimed to determine the prevalence and genetic basis of protein C and protein S deficiencies in Thai population. METHODS: Healthy volunteers were tested for protein C activity and free protein S antigen. Subjects with low values were requested for repeated testing and exclusion of acquired causes. Cases with persistently low levels were assayed for respective gene mutations using direct sequencing and multiplex ligation-dependent probe amplification (MPLA) when PROS1 point mutation was undetectable. RESULTS: For protein C activities (N = 5234), the values of men were lower than those of post-menopausal women (P < 0.001). In 17 of 18 subjects, there were 7 types of PROC mutations, 64.7% of which were p.R189W and 2 were previously unreported. Protein S levels (N = 5242) were highest in men, followed by post-menopausal and pre-menopausal women, respectively (P < 0.001). The repeatedly low protein S was mostly in female (88.2%). Among 29 subjects with protein S below the sex-specific 2.5 percentile cut-points, 4 types of mutations were found in 5 subjects (17.2%) with one previously unreported mutation. Free protein S levels were below 30 U/ml in all cases with mutations. The estimated prevalence of PROC and PROS1 mutations in Thai population was 0.69% and 0.22%, respectively. CONCLUSIONS: PROC mutations, especially p.R189W, are common in Thais. However, mildly depressed protein S levels were frequently found in women with undetectable PROS1 mutation.
INTRODUCTION: In contrast to Caucasians, hereditary anticoagulant deficiencies are more common in Asians and mutations are heterogeneous among different countries. This study aimed to determine the prevalence and genetic basis of protein C and protein S deficiencies in Thai population. METHODS: Healthy volunteers were tested for protein C activity and free protein S antigen. Subjects with low values were requested for repeated testing and exclusion of acquired causes. Cases with persistently low levels were assayed for respective gene mutations using direct sequencing and multiplex ligation-dependent probe amplification (MPLA) when PROS1 point mutation was undetectable. RESULTS: For protein C activities (N = 5234), the values of men were lower than those of post-menopausal women (P < 0.001). In 17 of 18 subjects, there were 7 types of PROC mutations, 64.7% of which were p.R189W and 2 were previously unreported. Protein S levels (N = 5242) were highest in men, followed by post-menopausal and pre-menopausal women, respectively (P < 0.001). The repeatedly low protein S was mostly in female (88.2%). Among 29 subjects with protein S below the sex-specific 2.5 percentile cut-points, 4 types of mutations were found in 5 subjects (17.2%) with one previously unreported mutation. Free protein S levels were below 30 U/ml in all cases with mutations. The estimated prevalence of PROC and PROS1 mutations in Thai population was 0.69% and 0.22%, respectively. CONCLUSIONS: PROC mutations, especially p.R189W, are common in Thais. However, mildly depressed protein S levels were frequently found in women with undetectable PROS1 mutation.
Authors: Thita Chiasakul; Elizabeth De Jesus; Jiayi Tong; Yong Chen; Mark Crowther; David Garcia; Chatree Chai-Adisaksopha; Steven R Messé; Adam Cuker Journal: J Am Heart Assoc Date: 2019-09-24 Impact factor: 5.501