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.IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease
Jae-Jung KIM ; Hea-Ji KIM ; Jeong Jin KIM ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Hong-Ryang KIL ; Gi Beom KIM ; Myung-Ki HAN ; Min Seob SONG ; Hyoung Doo LEE ; Hyun Ok JUN ; Kee Soo HA ; Young Mi HONG ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2021;51(3):267-278
Background and Objectives:
Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined.
Methods:
Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease.
Results:
Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022).
Conclusions
High IgA levels in patients with KD are prognostic for the risk of CALs.
6.Electrocardiographic Manifestations in Patients with COVID-19: Daegu in South Korea
Han-Joon BAE ; Hyun Jun CHO ; Chan-Hee LEE ; Myung Hwan BAE ; Hyoung-Seob PARK ; Byung Chun JUNG ; Dong-Gu SHIN ; Yongkeun CHO ; Jongmin HWANG ; Seongwook HAN ; Kyu-Hwan PARK ; Se Yong JANG ; Young Soo LEE
Korean Circulation Journal 2021;51(10):851-862
Background and Objectives:
As the coronavirus disease 2019 (COVID-19) spreads worldwide, cardiac injury in patients infected with COVID-19 becomes a significant concern. Thus, this study investigates the impact of several electrocardiogram (ECG) parameters and disease severity in COVID-19 patients.
Methods:
Seven medical centers in Daegu admitted 822 patients with COVID-19 between February and April 2020. This study examined 267 patients among them who underwent an ECG test and evaluated their biochemical parameters like C-reactive protein (CRP), log N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), cardiac enzyme, and ECG parameters (heart rate, PR interval, QRS interval, T inversion, QT interval, and Tpe [the interval between peak to end in a T wave]).
Results:
Those patients were divided into 3 groups of mild (100 patients), moderate (89 patients), and severe (78 patients) according to clinical severity score. The level of CRP, log NT-proBNP, and creatinine kinase-myocardial band were significantly increased in severe patients. Meanwhile, severe patients exhibited prolonged QT intervals (QTc) and Tpe (Tpe-c) compared to mild or moderate patients. Moreover, deceased patients (58; 21.7%) showed increased dispersion of QTc and Tpe-c compared with surviving patients (78.2±41.1 vs. 40.8±24.6 ms and 60.2±37.3 vs. 40.8±24.5 ms, both p<0.05, respectively). The QTc dispersion of more than 56.1 ms could predict the mortality in multivariate analysis (odd ratio, 11.55; 95% confidence interval, 3.746–42.306).
Conclusions
COVID-19 infections could involve cardiac injuries, especially cardiac repolarization abnormalities. A prolonged QTc dispersion could be an independent predictable factor of mortality.
7.IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease
Jae-Jung KIM ; Hea-Ji KIM ; Jeong Jin KIM ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Hong-Ryang KIL ; Gi Beom KIM ; Myung-Ki HAN ; Min Seob SONG ; Hyoung Doo LEE ; Hyun Ok JUN ; Kee Soo HA ; Young Mi HONG ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2021;51(3):267-278
Background and Objectives:
Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined.
Methods:
Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease.
Results:
Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022).
Conclusions
High IgA levels in patients with KD are prognostic for the risk of CALs.
8.Electrocardiographic Manifestations in Patients with COVID-19: Daegu in South Korea
Han-Joon BAE ; Hyun Jun CHO ; Chan-Hee LEE ; Myung Hwan BAE ; Hyoung-Seob PARK ; Byung Chun JUNG ; Dong-Gu SHIN ; Yongkeun CHO ; Jongmin HWANG ; Seongwook HAN ; Kyu-Hwan PARK ; Se Yong JANG ; Young Soo LEE
Korean Circulation Journal 2021;51(10):851-862
Background and Objectives:
As the coronavirus disease 2019 (COVID-19) spreads worldwide, cardiac injury in patients infected with COVID-19 becomes a significant concern. Thus, this study investigates the impact of several electrocardiogram (ECG) parameters and disease severity in COVID-19 patients.
Methods:
Seven medical centers in Daegu admitted 822 patients with COVID-19 between February and April 2020. This study examined 267 patients among them who underwent an ECG test and evaluated their biochemical parameters like C-reactive protein (CRP), log N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), cardiac enzyme, and ECG parameters (heart rate, PR interval, QRS interval, T inversion, QT interval, and Tpe [the interval between peak to end in a T wave]).
Results:
Those patients were divided into 3 groups of mild (100 patients), moderate (89 patients), and severe (78 patients) according to clinical severity score. The level of CRP, log NT-proBNP, and creatinine kinase-myocardial band were significantly increased in severe patients. Meanwhile, severe patients exhibited prolonged QT intervals (QTc) and Tpe (Tpe-c) compared to mild or moderate patients. Moreover, deceased patients (58; 21.7%) showed increased dispersion of QTc and Tpe-c compared with surviving patients (78.2±41.1 vs. 40.8±24.6 ms and 60.2±37.3 vs. 40.8±24.5 ms, both p<0.05, respectively). The QTc dispersion of more than 56.1 ms could predict the mortality in multivariate analysis (odd ratio, 11.55; 95% confidence interval, 3.746–42.306).
Conclusions
COVID-19 infections could involve cardiac injuries, especially cardiac repolarization abnormalities. A prolonged QTc dispersion could be an independent predictable factor of mortality.
9.Retroperitoneal Viscum album extract instillation in patients with a large amount of drainage after kidney transplantation
Young Jun PARK ; Sang Kyun MOK ; Jang Yong KIM ; Sang Seob YUN ; Sun Cheol PARK
Annals of Surgical Treatment and Research 2021;101(6):368-373
Purpose:
After kidney transplantation (KT), a large amount of drainage can delay postoperative recovery. Viscum album extract is an agent used in pleurodesis, and the purpose of this study was to evaluate the efficacy of this agent in reducing the amount of drainage after KT.
Methods:
Medical records of patients with a large amount of drainage (≥ 100 mL/day) on postoperative day (POD) 7 after KT who had undergone V. album extract instillation through drainage tube (n = 115) or conservative management (n = 177) were retrospectively reviewed. The primary endpoint was a decrease in the amount of drainage on POD 14 from POD 7.
Results:
A decrease in the amount of drainage on POD 14 from POD 7 was larger in the V. album extract instillation group than in the conservative management group (–228.3 ± 181.6 mL vs. –144.6 ± 202.0 mL, P < 0.001). Duration of hospitalization after operation was shorter in the V. album extract instillation group than in the conservative management group (15.9 ± 3.2 days vs. 18.1 ± 5.3 days, P < 0.001). In multivariate analysis, there was a statistically significant association of V. album extract instillation with lower risk of persistent large amount of drainage (≥ 100 mL/day on POD 14), with an odds ratio of 0.57 (95% confidence interval, 0.35–0.93; P = 0.026).
Conclusion
Retroperitoneal V. album extract instillation could be effective in reducing the amount of drainage and promoting postoperative recovery in patients with a large amount of drainage after KT.
10.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.

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