VKORC1 and CYP2C9 Genotype Variations in Relation to Warfarin Dosing in Korean Stroke Patients / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Variant alleles of CYP2C9 and VKORC1 account for differences in anticoagulation response. We sought to establish a warfarin dosing formula for individualized target International Normalization Ratio of Prothrombin Times (INRs) using data from single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 in Korean patients. METHODS: Ischemic stroke patients displaying stable target INR for at least 3 months before enrollment were analyzed. Warfarin and vitamin K levels were measured to adjust for confounders. Phenotypes were defined using the 'warfarin response index' (WRI) defined as INR divided by the daily maintenance warfarin dose. We tested SNPs in CYP2C9 (3 sites: 430C>T (rs1799853), 1075A>C (rs1057910), 1076T>C) and VKORC1 (14 sites: 381C>T, 861C>A (rs17880887), 2653G>C, 3673A>G, 5496G>T, 5808T>G (r17882154), 6009C>T, 6484T>C (rs9934438), 6853C>T (rs17886369), 7566T>C, 8767G>C, 8814T>C, 9041G>A (rs17880624), and 9071G>T) using a standard sequencing method. Multivariate linear regression analysis was applied to establish the formula for warfarin dosage. RESULTS: All 204 patients had excellent drug compliance. The mean INR was 2.22 (+0.56) and mean daily maintenance dose of warfarin was 3.92 mg (+1.54). Patients with low WRI were younger (PC, PC, 3673G>A, 6484T>C, 6853C>G. 7566C>T, 9041G>A) (r2=1). Based on these data, a warfarin dosing formula was established. CONCLUSIONS: WRI is influenced by age, body mass index and SNPs in VKORC1 and CYP2C9 in Korean stroke patients. The obtained warfarin dosing formula may be clinically applicable.

Evaluation of Cobas Integra 700 and Distribution of High Sensitivity C-reactive Protein Levels in Koreans / 대한진단검사의학회지

BACKGROUND: Prospective studies suggest that C-reactive protein (CRP) is a novel and indepen-dent risk factor of coronary heart disease. High-sensitivity methods for CRP (hs-CRP) measurement are needed for this purpose. In this study, we evaluated the performance of Cobas Integra 700 (Roche Diagnostics, Basel, Switzerland) and aimed to establish the distribution of serum CRP concentrations in healthy Koreans with the hs-CRP method. METHODS: The subjects of this study were 853 males (age; 45.9 +/- 9.8 years) and 546 females (age; 45.7 +/- 10.8 years) who visited the Health Promotion Center of the Asan Medical Center for routine health checks. Hs-CRP was measured with the Cobas Integra 700. The within-day precision, the between-day precision, the degree of correlation, the linearity, and the detection limit of hs-CRP were also analyzed with the Cobas Integra 700. RESULTS: The within-day coefficients of variation (CVs) were 0% and 1.3%. The between-day CVs were 4.0% and 3.0%. The percentage of relative nonlinearity was 0.78%. The correlation coefficient of the Cobas Integra 700 with the Behring Nephelometer was 0.994. The lower detection limit was 0.064 mg/L and the functional detection limit was 0.472 mg/L. The geometric mean concentration of CRP in Koreans was 0.69 mg/L. The mean CRP of the male population was 0.79 mg/L, which was higher than that of Korean females (0.54 mg/L) (P<0.0001). There was a significant trend to higher CRP values with increasing age (P<0.05). CONCLUSIONS: The linearity, the precision, the correlation, the detection limit of the Cobas Integra 700 were satisfactory. The age and sex-specific guidelines for hs-CRP would make the early intervention for coronary heart disease possible.

Correlations among Serum Lipoprotein (a), LDL cholesterol, and Apolipoprotein (a) Concentrations in Liver Cirrhosis / 대한임상병리학회지

BACKGROUND: The structure of lipoprotein(a) [Lp(a)] includes a low-density lipoprotein cholesterol (LDL-C) component and apolipoprotein(a) [apo(a)] linked to apolipoprotein B-100 of LDL-C with a disulfide bond. Liver cirrhosis is the only disease in which the decrease of serum Lp(a) concentra-tion is observed as a secondary effect. In this study, we tried to investigate the mechanisms for the Lp(a) decrease in cirrhotic patients. METHODS: Forty Child 's class A cirrhotic patients, 40 Child 's class C patients from Asan Medical Center, and 80 healthy controls were recruited. Serum concentrations of interleukin-6 (IL-6), LDL-C, Lp(a), and free apo(a) were measured. RESULTS: The serum concentrations of Lp(a) in the Child 's class C patients were significantly lower than those in class A and the control group (P < 0.05). The apo(a) concentrations in the Child 's class C patients were significantly lower than those in class A and the control group (P < 0.05). The LDL-C concentrations of Child 's class C patients were significantly lower than those in class A and the con-trol group (P < 0.01). The IL-6 concentrations of Child 's class C patients were significantly higher than those in class A and the control group (P < 0.005). Serum concentrations of Lp(a) showed positive correlations with those of LDL-C (r=0.42, P < 0.0001) and with those of the free apo(a) (r=0.68, P < 0.0001). But serum concentrations of IL-6 had no correlation to those of the Lp(a) or the free apo(a). CONCLUSIONS: Considering the positive correlation between Lp(a) and LDL-C, the decrease in the serum Lp(a) in cirrhotic patients could be due mainly to the decrease in the LDL component, although we could not suggest the mechanism for the LDL decrease.

Serum Osteocalcin and Urine Deoxypyridinoline Levels in Middle Aged Healthy Koreans; Age and Sex Related Variations / 대한임상병리학회지

BACKGROUND: Postmenopausal osteoporosis is the main problem in women, but senile osteoporosis is believed to occur after 65 years and affects men and women equally. Measurement of biochemical markers in conjunction with bone mineral density (BMD) determination can detect individual patients at the greatest risk of developing osteoporosis. METHODS: We measured serum osteocalcin levels as a bone formation marker, and urinary deoxypyridinoline (DPD) levels as a bone resorption marker, in 2190 men (from 22 to 83 year-old), and 1209 women (from 25 to 80 year-old). The age and sex related variations of serum osteocalcin and urinary DPD levels were analysed. The serum osteocalcin and urinary DPD levels were compared with BMD. These biochemical bone turnover markers were compared with each other. RESULTS: In women, serum osteocalcin and urinary DPD levels were increased with age from forties to sixties, after then showed decrease from seventies. In men, serum osteocalcin levels were slightly decreased with age, but DPD levels were slightly increased with age in men. These biochemical bone markers and BMD showed negative correlations. Osteocalcin and DPD levels showed positive correlations, especially in women. Osteocalcin levels were higher in men than women, age before fifth decades but lower in men than women after fifties. DPD levels was higher in women than men through all the age. CONCLUSION: Osteocalcin and DPD levels showed age and sex related variations in healthy Koreans. In management of patients with a risk of osteoporosis, consideration of variations according to the age and sex should be given.