PURPOSE: UGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs. MATERIALS AND METHODS: We directly sequenced 288 subjects consisting of 96 Korean, 48 Japanese, 48 Han Chinese, 48 African American, and 48 European American subjects. Subsequently, we analyzed genetic variability, linkage disequilibrium (LD) structures and ethnic differences for each gene. We also conducted in silico analysis to predict the function of novel SNPs. RESULTS: A total of 87 SNPs were detected, with seven pharmacogenetic core SNPs and 31 novel SNPs. We observed that the frequencies of UGT1A1 *6 (rs4148323), UGT1A1 *60 (rs4124874), UGT1A1 *93 (rs10929302), UGT2B7 *2 (rs7439366), a part of UGT2B7 *3 (rs12233719), and UGT2B15 *2 (rs1902023) were different between Asian and other ethnic groups. Additional in silico analysis results showed that two novel promoter SNPs of UGT1A1 -690G>A and -689A>C were found to potentially change transcription factor binding sites. Moreover, 673G>A (UGT2B7), 2552T>C, and 23269C>T (both SNPs from UGT2B15) changed amino acid properties, which could cause structural deformation. CONCLUSION: Findings from the present study would be valuable for further studies on pharmacogenetic studies of personalized medicine and drug response.
Asian Continental Ancestry Group/genetics ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency/genetics ; Glucuronosyltransferase/*genetics ; Haplotypes/genetics ; Humans ; Linkage Disequilibrium/genetics ; Male ; Polymorphism, Single Nucleotide/*genetics

Acute stent thrombosis after percutaneous coronary intervention (PCI) is still problematic because of the subsequent development of myocardial infarction and poor prognosis. The incidence of acute stent thrombosis, occurring within 0-24hours after PCI, is relatively low, but underlying causes and treatment strategy are not well defined. Multi-vessel disease, ST-elevated myocardial infarction (STEMI), and large thrombotic burden are known risk factors of acute stent thrombosis. Thrombus aspiration, balloon angioplasty and glycoprotein IIb/IIIa receptor blocker could be therapeutic options. Recently we experienced two cases of acute stent thrombosis which developed during PCI with the aggravation of chest pain, and acute stent thrombosis were diagnosed immediately and successfully treated. Here we report two cases of acute stent thrombosis during PCI for one patient with STEMI and the other with acute coronary syndrome, which were successfully treated with thrombus aspiration and intravenous infusion of glycoprotein IIb/IIIa receptor blocker.
Acute Coronary Syndrome* ; Angioplasty, Balloon ; Chest Pain ; Coronary Thrombosis ; Glycoproteins ; Humans ; Incidence ; Infusions, Intravenous ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prognosis ; Risk Factors ; Stents* ; Thrombosis*

This study was performed to evaluate the effects of diabetes on short- and mid-term clinical outcomes in patients with acute myocardial infarction (AMI). Between October 2005 and December 2009, a total of 22,347 patients with AMI from a nationwide registry was analyzed. At the time point of the day 30 after AMI onset, landmark analyses were performed for the development of major adverse cardiovascular events (MACEs), including death, re-infarction and revascularization. In this cohort, 6,131 patients (27.4%) had diabetes. Short-term MACEs, which occurred within 30 days of AMI onset, were observed in 1,364 patients (6.1%). Among the 30-day survivors (n = 21,604), mid-term MACEs, which occurred between 31 and 365 days after AMI onset, were observed in 1,181 patients (5.4%). After adjustment for potential confounders, diabetes was an independent predictor of mid-term MACEs (HR, 1.25; 95% CI, 1.08-1.45; P = 0.002), but not of short-term MACEs (HR: 1.16; 95% CI: 0.93-1.44; P = 0.167). Diabetes is a poor prognostic factor for mid-term clinical outcomes but not for short-term outcomes in AMI patients. Careful monitoring and intensive care should be considered in diabetic patients, especially following the acute stage of AMI.
Acute Disease ; Aged ; Cardiovascular Diseases/etiology ; Cohort Studies ; Diabetes Mellitus, Type 2/complications/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Myocardial Infarction/*diagnosis/epidemiology/mortality ; Prognosis ; Proportional Hazards Models ; Registries ; Survival Analysis ; Time Factors

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.
African Americans/genetics ; Alleles ; Amino Acids/metabolism ; Asian Continental Ancestry Group/genetics ; Dihydrouracil Dehydrogenase (NADP)/*genetics ; Ethnic Groups/*genetics ; European Continental Ancestry Group/genetics ; Fluorouracil/metabolism ; Gene Frequency ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.
African Americans/genetics ; Alleles ; Amino Acids/metabolism ; Asian Continental Ancestry Group/genetics ; Dihydrouracil Dehydrogenase (NADP)/*genetics ; Ethnic Groups/*genetics ; European Continental Ancestry Group/genetics ; Fluorouracil/metabolism ; Gene Frequency ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of CYP3A4*1B (rs2740574) and CYP3A5*3C (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of CYP3A4*18 (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.
Asian Continental Ancestry Group ; Computer Simulation ; Cytochrome P-450 Enzyme System ; DNA ; Gene Frequency ; Genotype ; Humans ; Precision Medicine ; Mass Screening* ; Pharmacogenetics ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Prescriptions

This study was conducted to assess the relationship between estimated glomerular filtration rate (eGFR) and bone mineral density (BMD) in Korean postmenopausal women with mild renal dysfunction. A total of 328 postmenopausal women who underwent BMD measurement during health check-up was investigated. BMD was measured in lumbar spine (L1-L4), femoral neck, total proximal femur and femoral trochanteric areas by dual energy radiography absorptiometry and renal function was estimated by eGFR using Cockcroft-Gault equation. Of the 328 subjects, 317 (96.6%) had an eGFR > or =60 mL/min/1.73 m2. By using simple linear regression analysis, age, height, weight and eGFR were significantly associated with BMD for the 4 aforementioned anatomic sites, while serum levels of creatinine and blood urea nitrogen did not influence BMD. When multiple regression analyses were applied, age and body weight still had significant associations with BMD at 4 different anatomic sites (P < 0.001). A significant association of eGFR with BMD remained in the lumbar spine, femoral neck and proximal total femur (P < 0.05) but not in the trochanteric area (P = 0.300). Our study suggests that a decline of renal function is associated with lower BMD in the lumbar spine, femoral neck and total proximal femur areas in Korean menopausal women with mild renal dysfunction.
Absorptiometry, Photon ; Aged ; Blood Urea Nitrogen ; *Bone Density ; Creatinine/blood ; Female ; Femur Neck/physiology ; *Glomerular Filtration Rate ; Humans ; Kidney Diseases/*physiopathology ; Kidney Function Tests ; Lumbar Vertebrae/physiology ; Middle Aged ; Osteoporosis, Postmenopausal/*physiopathology ; Republic of Korea

It is known that there is a marked variation in the frequency of variant angina attacks according to the circadian rhythm. The attack frequency is usually highest in the early morning and lowest in the afternoon. We describe here a middle-aged woman with variant angina whose chest pain occurred only during daytime. Because of her job, she sleeps from noon to 6 pm, and she experienced chest pain only during 2 to 3 pm. These findings suggest that the alterations to the sleep and wake cycle can affect the circadian variation of variant angina.
Chest Pain ; Circadian Rhythm ; Female ; Humans

BACKGROUND AND OBJECTIVES: Some patients stop statin therapy in spite of their doctors' advice. This study was designed to assess the pattern of lipoprotein profile changes and clinical characteristics of the patients who discontinued statin therapy. SUBJECTS AND METHODS: 69 patients (male 42.0%) were enrolled. The clinical characteristics and laboratory data on the lipoprotein levels were obtained from the medical records. RESULTS: The coexistence of diabetes mellitus (DM) was seen in 28% of the patients, hypertension was noted in 72% and coronary artery disease (CAD) was noted in 42%. The average lipoprotein levels during statin therapy were total cholesterol (TC)=163.8 mg/dL, triglycerides (TG)=174.3 mg/dL, high-density lipoprotein cholesterol (HDL-C)=34.8 mg/dL and low-density lipoprotein cholesterol (LDL-C)=94.2 mg/dL. LDL-C level increased by 44.9% at 2-3 months after ceasing statin therapy and by 54.6% at 4-6 months after ceasing statin therapy (p<0.01). The changes of the lipoprotein levels from baseline to 2-3 months and 4-6 months after discontinuation were +22.6% and +30.0% for the TC level, +20.8% and +24.0% for the TG level, and 0.06% and -0.65% for the HDL-C level respectively (p<0.01 for TC and TG, p=not significant (NS) for HDL-C). The achievement rate of target LDL-C level as suggested by the Adult Treatment Panel III (ATP III) of National Cholesterol Education Program (NCEP) was decreased 62.7% at 2-3 months and then it was decreased to 61.8% at 4-6 months after statin discontinuation. DM and CAD were more frequent in the patients who did not achieve the target LDL-C level even with life style modification. CONCLUSION: After statin discontinuation, TC and LDL-C were increased within 3 months. DM and CAD were highly prevalent in patients who didn't achieve their treatment goal.
Achievement ; Adult ; Cholesterol ; Coronary Artery Disease ; Diabetes Mellitus ; Humans ; Hypertension ; Life Style ; Lipoproteins ; Medical Records ; Triglycerides

Congenital cystic adenomatoid malformation(CCAM) is one of the most common congenital lung lesions. Clinical manifestations that show are neonatal respiratory distress, recurrent respiratory infection, pneumothorax, and hemothorax. But, there are patients who are asymptomatic until mid-childhood. The treatment of asymptomatic CCAM is controversial. There is a possibility to resolve it spontaneously, but late complications such as recurrent pulmonary infection, pneumothorax, hemothorax, and cancer, which includes bronchoalveolar carcinoma and rhabdomyocarcinoma, pleuropulmonary blastoma still remain. Some investigators advocate routine surgery for all cases of CCAM that are apparent at birth. A previously healthy 16-months-old girl who had suffered from a cough for 2 weeks was transferred to Asan Medical Center with CCAM. Due to a chest CT and fever, we first thought that she had CCAM with infection. After we treated her with antibiotics for one week, we performed surgery to confirm the diagnosis and to prevent further complication. But by surgical wedge resection, a pleuropulmonary blastoma was found. There were no evidence of metastasis and adjacent involvement. She started her chemotherapy with vincristine, actinomycin D and cyclophosphamide, and is now continuing maintenance chemotherapy with etoposide, vincristine, and Ifosfamide. We report pleuropulmonary blastoma that presented as CCAM. So we recommend surgical resection in asymptomatic CCAM to confirm the diagnosis and to prevent its malignant transformation, even not accompanied by symptoms.
Anti-Bacterial Agents ; Child ; Chungcheongnam-do ; Cough ; Cyclophosphamide ; Cystic Adenomatoid Malformation of Lung, Congenital* ; Dactinomycin ; Diagnosis ; Drug Therapy ; Etoposide ; Female ; Fever ; Hemothorax ; Humans ; Ifosfamide ; Lung ; Maintenance Chemotherapy ; Neoplasm Metastasis ; Parturition ; Pneumothorax ; Research Personnel ; Tomography, X-Ray Computed ; Vincristine