1.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
2.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
3.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
4.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
Background and Objectives:
Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients.
Methods:
A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases).
Results:
Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD.
Conclusions
A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.
5.Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population
Jeong Jin YU ; Hee Joung CHOI ; Hwa Jin CHO ; Sung Hye KIM ; Eun Jung CHEON ; Gi Beom KIM ; Lucy Youngmin EUN ; Se Yong JUNG ; Hyun Ok JUN ; Hyang-Ok WOO ; Sin-Ae PARK ; Soyoung YOON ; Hoon KO ; Ji-Eun BAN ; Jong-Woon CHOI ; Min Seob SONG ; Ji Whan HAN
Journal of Korean Medical Science 2024;39(16):e144-
Background:
This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice.
Methods:
This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit.
Results:
Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula.
Conclusion
A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.
6.Cognitive Behavioral Therapy for Tinnitus: Outpatient-Based Treatment
Jong-Geun LEE ; Yongmin CHO ; Hyunseok CHOI ; Gi Hwan RYU ; Jaeman PARK ; Dongha KIM ; Sung-Won CHAE ; Jae-Jun SONG
Korean Journal of Otolaryngology - Head and Neck Surgery 2024;67(5):270-276
Background and Objectives:
Cognitive behavioral therapy (CBT) is a treatment option for subjective tinnitus. There are many reports on its clinical efficacy, but the protocol has not been well established. The purpose of this study was to set an outpatient-based CBT protocol and evaluate its clinical efficacy for tinnitus.Subjects and Method A total of 85 chronic tinnitus patients was assessed in this prospective study. After evaluating for eligibility, 30 patients completed CBT based on a protocol of 5 weekly sessions in an outpatient setting. Therapeutic efficacy was assessed by Tinnitus Handicap Inventory (THI) questionnaires and visual analogue scale (VAS) for tinnitus. The initial scores were compared with the final scores, which were assessed a month after the fifth CBT session.
Results:
The results showed that CBT reduced THI and VAS scores significantly (p<0.05).
Conclusion
The results of the study suggest that an outpatient-based CBT protocol can be clinically beneficial for patients with tinnitus.
7.Clonazepam Usage Improves Chronic Tinnitus and Sleep Quality: A Prospective Cohort Study
Hyeon Geun KIM ; Ho Young LEE ; Euyhyun PARK ; June CHOI ; Yoon Chan RAH ; Jae Jun SONG ; Sung Won CHAE ; Hak Hyun JUNG ; Gi Jung IM
Korean Journal of Otolaryngology - Head and Neck Surgery 2022;65(12):758-764
Background and Objectives:
Tinnitus, although being a common chronic disease, can be an intractable disease that causes depression and insomnia. This study aimed to analyze the results of the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI) questionnaire surveys before and after clonazepam therapy. In addition, we analyzed the association of three pre-treatment questionnaires and evaluated whether pre-treatment factors could predict the post-treatment THI index.Subjects and Method Patients were selected from those who visited a tertiary hospital from 2019 to 2021 for the treatment of chronic tinnitus they had for more than 3 months and who were over 20 years old. Patients were excluded from the study if they were diagnosed with acute sudden hearing loss, Meniere’s disease, brain/internal auditory canal tumors, or muscular/vascular tinnitus. The questionnaire surveys of THI, BDI, PSQI were conducted before and after 3 months of clonazepam therapy (Rivotril [Roche Inc.] 0.25 or 0.5 mg). Questionnaire scores were compared using the paired t-test. Multiple regression analysis was used to determine the relationships among the three questionnaires.
Results:
A total of 76 patients (38 males and 38 females) with the mean age of 57.2±9.01 years was analyzed. The average hearing threshold was 30.4±20.67 dB HL on the right and 31.7±17.06 dB HL on the left. The pre-treatment THI, BDI, and PSQI scores were 44.3±23.4, 7.96±2.36, and 6.85±4.68, respectively. The relationships between the THI and BDI and the THI and PSQI were significant (p=0.0027 and p<0.0001, respectively). The pre-THI score showed no significant association with age, sex, or hearing threshold (p=0.91, 0.85, and 0.23, respectively). The post-treatment THI score was 33.6±17.1, which was significantly lower than the pre-THI scores (p<0.0001). Post-BDI and post-PSQI were 7.38±2.25 and 4.04±3.20, respectively. Post-PSQI also significantly decreased compared with pre-PSQI (p=0.0002), but post-BDI did not significantly decrease (p=0.1231). In the THI survey, Question 7 (sleep disturbance) showed decrease the most, followed by Question 25 (unstable mood). The post-treatment THI could be predicted by using the formula, 0.7673+0.6947×pre-THI+0.3572×pre-PSQI.
Conclusion
The appropriate/optional use of clonazepam at low doses (0.25-0.5 mg) can significantly improve chronic tinnitus and sleep quality. Tinnitus was significantly associated with the scores of THI, BDI, PSQI and the usage of Clonazepam significantly reduced the THI and PSQI scores. However, clonazepam did not affect the BDI score.
8.Identification of rare coding variants associated with Kawasaki disease by whole exome sequencing
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Byung-Ok CHOI ; Yeon-Mok OH ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Genomics & Informatics 2021;19(4):e38-
Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18–4.41; p = 0.0027–0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89–37.3; p = 0.0058–0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.
9.Change in Self-Evaluation of Hearing Status According to Age: A Population-Based Study
Seok-Youl CHOI ; Jee Won MOON ; June CHOI ; Jae-Jun SONG ; Gi Jung IM ; Sung-Won CHAE
Korean Journal of Otolaryngology - Head and Neck Surgery 2021;64(12):861-867
Background and Objectives:
Self-reported hearing levels determined by self-report questionnaires are not always correlated with the audiometric hearing level. It is necessary to ascertain the subjectively perceived normal hearing threshold to determine the need for hearing aids at the appropriate time. The objective is to identify the level of correlation between the self-reported hearing level and the audiometric hearing level and ascertain the subjectively perceived normal hearing threshold for each age group.Subjects and Method This cross-sectional study, using the data from the Korea National Health and Nutrition Examination Survey V, looked at participants with hearing loss who were aged ≥40 years. Pure tone audiometry was conducted bilaterally. Self-reported hearing level was ascertained via survey enquiring about hearing loss. The level of correlation between self-reported hearing level and audiometric hearing level, age-specific patterns of hear-ing self-evaluation and subjectively perceived normal hearing values at which participants complained of hearing loss were main outcomes.
Results:
Mean audiometric thresholds (MATs) increased with the age and degree of self-reported hearing level. The accuracy of self-reported hearing level compared to the audiometric threshold decreased with age both in the better-ear and worse-ear groups. Younger participants tended to overestimate their hearing impairment, while older participants tended to underestimate it. Subjectively perceived normal hearing thresholds increased with age and they were very close to the MATs for each age group.
Conclusion
Results can be useful for devising different age-group specific pure tone audi-ometry-based diagnostic criteria for self-reported hearing loss, which can be used to determine the need for hearing aid in a timely manner.
10.Cognitive Behavioral Therapy in Korean Tinnitus Patients
Angela Yun KIM ; Gi-Hwan RYU ; Hyunseok CHOI ; June CHOI ; Gi Jung IM ; Sung-Won CHAE ; Jae-Jun SONG
Korean Journal of Otolaryngology - Head and Neck Surgery 2021;64(11):844-850
Cognitive behavioral therapy, first introduced by Beck in the 1950s to treat depression by integrating cognitive and behavioral therapies, is now an established psychotherapy technique used to treat insomnia, chronic pain, and anxiety. Currently, cognitive behavioral therapy is widely used to treat tinnitus in European countries, and the efficacy and safety of the treatment have been proven through randomized clinical trials and meta-analyses. Although interest in cognitive behavioral therapy for tinnitus is increasing in Korea, there are limited reports. Because many studies so far have targeted patients in Western countries, it is difficult to apply the same to domestic patients due to cultural and linguistic differences, the absence of standardized guidelines, and limitations in clinic hours. We experienced various cases in which tinnitus was effectively treated simultaneously with pharmacotherapy and cognitive behavioral therapy, so here we report an introduction to the program along with a literature review. Cognitive behavioral therapy was performed as a 4-week program in our hospital, and progress was evaluated through Visual Analogue Scales (VAS) and tinnitus handicap inventory (THI). After each weekly 20-minute individual counseling session, a take-home writing task was given to the patient. The main goal was to guide the patient to discover and correct automatic thoughts related to their tinnitus symptoms. This paper aimed to introduce a specific scheme on how to perform cognitive behavioral therapy for domestic tinnitus patients.

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