Natural anticoagulant deficiencies in Thais: A population-based study

Abstract

IntroductionIn 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. MethodsHealthy 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. ResultsFor 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. ConclusionsPROC mutations, especially p.R189W, are common in Thais. However, mildly depressed protein S levels were frequently found in women with undetectable PROS1 mutation.