BACKGROUND AND OBJECTIVES: Analyzing the association between multiple SNPs and the disease outcomes will provide new insight into the disease's etiology. However, this presents an analytic difficulty due to the large number of SNPs and the complex relationships among them. We proposed using the mixed model approach to identify the significant multi-locus genotypes and the high-order gene-to-gene interactions. SUBJECTS AND METHODS: We described the mixed effects model and applied this approach to real world data. For the purpose of these analyses, we examine the association of four types of SNPs (AGT5, APOB, CETP3 and ACE6) with the lipid profiles and the measures related with cardiovascular disease. We used data from 672 healthy individuals (283 males and 389 females) who were without cardiovascular diseases. RESULTS: The results of our analysis suggested that there were significant random genotype patterns and genotype groups according to the gender effect on the lipid profiles. In other words, there was significant variability across the genotype groups because of the effect of gender on the lipid profiles. CONCLUSION: The mixed model approach provided a flexible statistical framework for controlling potential confounding variables and for identifying a significant genetic contributions that may come about through the effects of multi-locus genotypes or through an interaction between the genotype and environmental variables (e.g. gender) with the variations in quantitative traits (e.g. lipid profiles). There were significant genetic contributions to the variability in the lipid profiles, and these were explained by the 4 SNPs described in our real data.
Apolipoproteins B ; Cardiovascular Diseases ; Confounding Factors (Epidemiology) ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide

BACKGROUND AND OBJECTIVES : The common methods of genetic association analysis are sensitive to population stratification, which may easily lead to a spurious association result. We used a regression approach based for linkage disequilibrium to perform a high resolution genetic association analysis. SUBJECTS AND METHODS : We applied a regression approach that can increase the resolution of quantitative traits that are related with cardiovascular diseases. The population data was composed of 543 males and 876 females without cardiovascular diseases, and it was obtained from a cardiovascular genome center. We used information about linkage disequilibrium between the marker and trait locus, and we added the covariates to model their effects. RESULTS : We found that this regression approach has the merit of analyzing genetic association based on linkage disequilibrium. In the analysis of the male group, the total cholesterol was significantly in linkage disequilibrium with CETP3 (p=0.002), and triglyceride was significantly in linkage disequilibrium with ACE8 (p=0.037), APOA1-1 (p=0.031), APOA5-1 (p=0.001), APOA5-2 (p=0.001) and LIPC4 (p=0.022). HDL-cholesterol was significantly in linkage disequilibrium with ACE7 (p=0.002), ACE8 (p=0.008), ACE10 (p=0.003), APOA5-2 (p=0.022), and MTP1 (p=0.001). In the female group, total cholesterol was significantly associated with APOA5-1 (p=0.020), APOA5-2 (p=0.001), and LIPC1 (p=0.016), and triglyceride was significantly associated with APOA5-1 (p=0.009), APOA5-2 (p=0.001), and CETP5 (p=0.049). LDL-cholesterol was significantly associated with APOA5-2 (p=0.004), and HDL-cholesterol was significantly associated with LIPC1 (p=0.004). CONCLUSION : We used a regression-based method to perform high resolution linkage disequilibrium analysis of a quantitative trait locus that's associated with lipid profiles. This method of using a single marker, as applied in this paper, was well suited for analysis of genetic association. Because of the simplicity, the method can also be easily performed by routine statistical analysis software.
Cardiovascular Diseases ; Cholesterol ; Female ; Genome ; Humans ; Linkage Disequilibrium* ; Male ; Quantitative Trait Loci* ; Triglycerides

Purpose: To proceed effectively with clinical research requires an understanding of the fundamental principles of study design and biostatistical methods. In this article, we identified and summarized basic clinical research designs and some of the key biostatistical methods that have been commonly used in clinical research. Materials and Methods: In an observational study, cross-sectional, case- control and Cohort designs were illustrated and compared. In a clinical trial study, parallel group design and cross-over designs were described according to their characteristics. Also, the biostatistical methods for their usages classified and summarized. Results: Understanding and evaluating research design are part of the process researchers must use to determine both the quality and usefulness of their research. Adequate applications to biostatistical methods are need; i.e., descriptive statistics, Student's t-test, ANOVA, nonparametrics, categorical data analysis, correlation and regression, and survival analysis. Conclusions: Research findings are used by clinical researcher to guide their practice and reduce their uncertainty in clinical decision making. However, to understand how to interpret research results, it is important to be able to understand basic statistical concepts and types of study design. Clinicians should also appropriately choose the biostatistical methods to suit their purposes.
Biostatistics ; Cohort Studies ; Cross-Over Studies ; Decision Making ; Observational Study ; Research Design* ; Statistics as Topic ; Uncertainty

BACKGROUND AND OBJECTIVES: It is very important to distinguish between the primary and secondary genetic effects at different sites within a small genetic region. Therefore, we evaluated the relative effects of single nucleotide polymorphisms (SNPs) within a gene on the serum lipid profiles by using individual data. SUBJECTS AND METHODS: To evaluate the contributions of SNPs in a region to the serum lipid profiles (total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein), we used data that consisted of 808 individuals (327 males and 481 females) who did not have cardiovascular disease. In this study, we used a stepwise regression procedure to analyze the relative effects of four single nucleotide polymorphisms (ACE6, ACE7, ACE8, ACE10) in a gene region on the development of the serum lipid profiles in each gender group. RESULTS: In the males, there were epistatic interaction effects between two loci (ACE6xACE7, ACE6xACE8, ACE6xACE10, ACE8xACE10 and ACE7xACE8) and among three loci (ACE6xACE7xACE8, ACE6xACE7xACE10 and ACE6xACE8xACE10). Also, there are interaction effects between two loci (ACE6xACE7, ACE6xACE8, ACE6xACE10, ACE7xACE10 and ACE8xACE10) and among three loci (ACE6xACE7xACE8, ACE6xACE7xACE10, ACE6xACE8xACE10 and ACE7xACE8xACE10) in the females. CONCLUSION: The results suggested that each of these loci is important in causing a relative change of the serum lipid profiles, even with simultaneously accounting for the effects at the other loci. In the results of the analysis, there existed the effects of individual loci and significant interaction between the loci on the serum lipid profiles in each gender group. It was confirmed that this stepwise regression method can be suitable for evaluating the relative effects of SNPs and it is easily performed.
Cardiovascular Diseases ; Cholesterol ; Female ; Genes, vif* ; Humans ; Linear Models* ; Lipoproteins ; Male ; Peptidyl-Dipeptidase A ; Polymorphism, Single Nucleotide* ; Triglycerides

PURPOSE: Rotavirus is an enteric pathogen that affects millions of children globally each year. But no specific therapy is available for the management of rotavirus diarrhea. Due to the clear need to define improved modality for treatment of rotavirus diarrhea, we evaluated the efficacy of anti- rotavirus IgY in the treatment of infants and children with gastroenteritis. METHODS: First, the amount of viral particle in the stools of thirteen patients (seven were given IgY, 6 placebo) infected by rotavirus were evaluated for 3 days with the quantitative RT-PCR method. Second, 36 children with known rotavirus infection identified by ELISA or semi-quantitative RT- PCR were evaluated. We gave 5 g anti-rotavirus egg yolk daily in two equally divided doses for 3 days to two groups (an 18 IgY group and an 18 placebo group), respectively after parenteral consent. Daily vomiting frequency, stool frequency, oral intake and urine output were monitored for 3 days, and electrolyte and blood chemistry were checked at the first and third days. RESULTS: First, in the placebo group, the amount of virus particles increased daily, but in the IgY group it decreased daily. Second, when IgY and placebos were given to children infected with rotavirus, diarrhea on the third day decreased significantly in the IgY group, compared with the placebo group. CONCLUSION: Treatment with antirotavirus immunoglobulin from immunized chicken's egg resulted in a decrease in the amount of viral particles in stools and diarrhea frequency in children. These results suggest that anti-rotavirus IgY is effective in the treatment of rotavirus gastroenteritis.
Infant ; Child ; Male ; Female ; Humans

Paraquat intoxication is a fatal problem. Most of paraquat intoxications happen through oral administration. But there is no clinical data for parenteral paraquat intoxication, so we will describe its fatal progression and clinical course. A 52-year-old male injected paraquat solution on his thigh. Initial serum level of paraquat was 42.7 microgram/mL and urgent hemoperfusion was performed and his serum level of paraquat was reduced by 5.2 microgram/mL. But the patient expired due to respiratory failure and hypoxemia. Different from oral paraquat poisoning, serum level of the drug increases rapidly in intramuscular intoxication. So the paraquat in blood rapidly accumulates in tissue, especially lung parenchyme. We removed his paraquat in blood rapidly, but could not get rid of tissue concentration, so we lost him even with lowered serum paraquat level. Through this case, it is thought that the paraquat intoxication via intramuscular injection can make up a extremely poor prognosis even with very a little amount of paraquat.
Administration, Oral ; Anoxia ; Hemoperfusion ; Humans ; Injections, Intramuscular* ; Lung ; Male ; Middle Aged ; Paraquat* ; Poisoning ; Prognosis ; Respiratory Insufficiency ; Thigh

Twelve strains of V. vulnificus isolated from clinical specimens in 2002~2004 in Jeollado province were determined for their biologic groups, serotypes, presence of vvhA (hemolysin/cytolysin) gene, DNA sequence, and PFGE patterns of NotI-restricted genomic DNA. The following results were obtained. All 12 isolates were biogroup 1, and API 20E profiles were: 5146105 for 5 (41.7%) isolates, and 5148125 for 2 isolates with sucrose fermentation. Ten (83.3%) of the 12 isolates was V. vulnificus serotype O4A, and two sucrose-fermenting isolates belonged to serotype O2. Alleles of cytolysin-hemolysin gene were detected in all 12 isolates. The nucleotide sequences of vvhA genes from strains WKHC 212 and WKHC 221 showed 94~97% similarity compared with those from previously reported 7 strains, YJ016, CMCP6, L-180, CDC B3547, IF Vv10, CIP 75.4T and CNRVC 970121. PFGE of NotI-restricted genomic DNA from the 12 isolates showed approximately 48.5 to 873-kb fragments and they were clustered to five (A to E) patterns. Two sucrose-fermenting isolates belonged to pattern D with 95% similarity with each other. Two strains isolated from two different patients had two identical patterns C and D. It is concluded that sucrose-fermenting strains also exist among clinical isolates of V. vulnificus in Korea, and they can be identified by using API 20E system, and by detecting vvhA gene. DNA sequences and PFGE pattern of NotI-restricted genomic DNA suggested that the two sucrose-fermenting isolates belonged to an identical clone, and two strains each isolated from two different patients belonged to two identical clones.
Alleles ; Base Sequence ; Centers for Disease Control and Prevention (U.S.) ; Clone Cells ; DNA ; Fermentation ; Humans ; Korea ; Sucrose ; Vibrio vulnificus* ; Vibrio*

BACKGROUND AND OBJECTIVES: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. METHODS: We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. RESULTS: BLK and FCGR2A were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10⁻¹¹ for BLK, and OR, 1.26; p=1.42×10⁻⁴ for FCGR2A). However, in KD subgroup analysis, we found that neither BLK nor FCGR2A were associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLK was associated with all KD subgroups, whereas FCGR2A was specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10⁻⁵). CONCLUSIONS: KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD.
Biomarkers ; Diagnosis ; Genetic Heterogeneity ; Genome-Wide Association Study ; Humans ; Male ; Mucocutaneous Lymph Node Syndrome ; Polymorphism, Single Nucleotide ; Population Characteristics ; Protein-Tyrosine Kinases

PURPOSE: The most common risk factor for fecal incontinence (FI) is obstetric injury. FI affects 1.4%–18% of adults. Most patients are unaware when they are young, when symptoms appear suddenly and worsen with aging. Autologous fat graft is widely used in cosmetic surgical field and may substitute for injectable bulky agents in treating FI. Authors have done fat graft for past several years. This article reports the effectiveness of the fat graft in treating FI and discusses satisfaction with the procedure. METHODS: Fat was harvested from both lateral thighs using 10-mL Luer-loc syringe. Pure fat was extracted from harvests and mixed with fat, oil, and tumescent through refinement. Fats were injected into upper border of posterior ano-rectal ring, submucosa of anal canal and intersphincteric space. Thirty-five patients with FI were treated with this method from July 2016 to February 2017 in Busan Hangun Hospital. They were 13 male (mean age, 60.8 years) and 22 female patients (mean age, 63.3 years). The Wexner score was checked before procedure. We evaluated outcome in outpatients by asking the patients. For 19 patients we checked the Wexner score after procedure. RESULTS: Symptom improved in 29 (82.9%), and not improved in 6 (17.1%). In 2 of 6 patients, they felt better than before procedure, although not satisfied. No improvement in 4. Mean Wexner score was 9.7 before procedure. There were no serious complications such as inflammation or fat embolism. CONCLUSION: Autologous fat graft can be an effective alternative treatment for FI. It is safe and easy to perform, and cost effective.
Adult ; Aging ; Anal Canal ; Busan ; Embolism, Fat ; Fats ; Fecal Incontinence ; Female ; Humans ; Inflammation ; Male ; Methods ; Outpatients ; Risk Factors ; Syringes ; Thigh ; Transplants

BACKGROUND AND OBJECTIVES: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. METHODS: We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. RESULTS: BLK and FCGR2A were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10⁻¹¹ for BLK, and OR, 1.26; p=1.42×10⁻⁴ for FCGR2A). However, in KD subgroup analysis, we found that neither BLK nor FCGR2A were associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLK was associated with all KD subgroups, whereas FCGR2A was specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10⁻⁵). CONCLUSIONS KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD.