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The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients

Background: Kawasaki disease (KD) is an acute, self-limited vasculitis disorder of unknown etiology in children. Immunologic abnormalities were detected during the acute phase of KD, which reflected that the effect cells of the activated immune system markedly increased cytokine production. High-dos...

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Autores principales: Yu, Hongyan, Liu, Fucheng, Chen, Kaining, Xu, Yufen, Wang, Yishuai, Fu, Lanyan, Zhou, Huazhong, Pi, Lei, Che, Di, Li, Hehong, Gu, Xiaoqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257007/
https://www.ncbi.nlm.nih.gov/pubmed/35812738
http://dx.doi.org/10.3389/fgene.2022.868159
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author Yu, Hongyan
Liu, Fucheng
Chen, Kaining
Xu, Yufen
Wang, Yishuai
Fu, Lanyan
Zhou, Huazhong
Pi, Lei
Che, Di
Li, Hehong
Gu, Xiaoqiong
author_facet Yu, Hongyan
Liu, Fucheng
Chen, Kaining
Xu, Yufen
Wang, Yishuai
Fu, Lanyan
Zhou, Huazhong
Pi, Lei
Che, Di
Li, Hehong
Gu, Xiaoqiong
author_sort Yu, Hongyan
collection PubMed
description Background: Kawasaki disease (KD) is an acute, self-limited vasculitis disorder of unknown etiology in children. Immunologic abnormalities were detected during the acute phase of KD, which reflected that the effect cells of the activated immune system markedly increased cytokine production. High-dose intravenous immunoglobulin (IVIG) therapy is effective in resolving inflammation from KD and reducing occurrence of coronary artery abnormalities. However, 10%–20% of KD patients have no response to IVIG therapy, who were defined as IVIG resistance. Furthermore, these patients have persistent inflammation and increased risk of developing coronary artery aneurysm (CAA). EIF2AK4 is a stress sensor gene and can be activated by pathogen infection. In addition, the polymorphisms of EIF2AK4 were associated with various blood vessel disorders. However, it remains unclear whether the EIF2AK4 gene polymorphisms were related to IVIG therapy outcome in KD patients. Methods: EIF2AK4/rs4594236 polymorphism was genotyped in 795 IVIG response KD patients and 234 IVIG resistant KD patients through TaqMan, a real-time polymerase chain reaction. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between EIF2AK4/rs4594236 polymorphism and IVIG therapeutic effects. Results: Our results showed that the EIF2AK4/rs4594236 AG/GG genotype was significantly associated with increased risk to IVIG resistance compared to the AA genotype (AG vs. AA: adjusted ORs = 1.71, 95% CIs = 1.17–2.51, and p = 0.0061; GG vs. AA: adjusted ORs = 2.09, 95% CIs = 1.36–3.23, and p = 0.0009; AG/GG vs. AA: adjusted ORs = 1.82, 95% CIs = 1.27–2.63, and p = 0.0013; and GG vs. AA/AG: adjusted ORs = 1.45, 95% CI = 1.04–2.02, and p = 0.0306). Furthermore, the stratified analysis of age and gender in the KD cohort indicated that male patients carrying the rs4594236 AG/GG genotype tends to be more resistant to IVIG therapy than female patients. Conclusion: These results suggested that EIF2AK4/rs4594236 polymorphism might be associated with increased risk of IVIG resistance in southern Chinese KD patients.
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spelling pubmed-92570072022-07-07 The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients Yu, Hongyan Liu, Fucheng Chen, Kaining Xu, Yufen Wang, Yishuai Fu, Lanyan Zhou, Huazhong Pi, Lei Che, Di Li, Hehong Gu, Xiaoqiong Front Genet Genetics Background: Kawasaki disease (KD) is an acute, self-limited vasculitis disorder of unknown etiology in children. Immunologic abnormalities were detected during the acute phase of KD, which reflected that the effect cells of the activated immune system markedly increased cytokine production. High-dose intravenous immunoglobulin (IVIG) therapy is effective in resolving inflammation from KD and reducing occurrence of coronary artery abnormalities. However, 10%–20% of KD patients have no response to IVIG therapy, who were defined as IVIG resistance. Furthermore, these patients have persistent inflammation and increased risk of developing coronary artery aneurysm (CAA). EIF2AK4 is a stress sensor gene and can be activated by pathogen infection. In addition, the polymorphisms of EIF2AK4 were associated with various blood vessel disorders. However, it remains unclear whether the EIF2AK4 gene polymorphisms were related to IVIG therapy outcome in KD patients. Methods: EIF2AK4/rs4594236 polymorphism was genotyped in 795 IVIG response KD patients and 234 IVIG resistant KD patients through TaqMan, a real-time polymerase chain reaction. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between EIF2AK4/rs4594236 polymorphism and IVIG therapeutic effects. Results: Our results showed that the EIF2AK4/rs4594236 AG/GG genotype was significantly associated with increased risk to IVIG resistance compared to the AA genotype (AG vs. AA: adjusted ORs = 1.71, 95% CIs = 1.17–2.51, and p = 0.0061; GG vs. AA: adjusted ORs = 2.09, 95% CIs = 1.36–3.23, and p = 0.0009; AG/GG vs. AA: adjusted ORs = 1.82, 95% CIs = 1.27–2.63, and p = 0.0013; and GG vs. AA/AG: adjusted ORs = 1.45, 95% CI = 1.04–2.02, and p = 0.0306). Furthermore, the stratified analysis of age and gender in the KD cohort indicated that male patients carrying the rs4594236 AG/GG genotype tends to be more resistant to IVIG therapy than female patients. Conclusion: These results suggested that EIF2AK4/rs4594236 polymorphism might be associated with increased risk of IVIG resistance in southern Chinese KD patients. Frontiers Media S.A. 2022-06-22 /pmc/articles/PMC9257007/ /pubmed/35812738 http://dx.doi.org/10.3389/fgene.2022.868159 Text en Copyright © 2022 Yu, Liu, Chen, Xu, Wang, Fu, Zhou, Pi, Che, Li and Gu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yu, Hongyan
Liu, Fucheng
Chen, Kaining
Xu, Yufen
Wang, Yishuai
Fu, Lanyan
Zhou, Huazhong
Pi, Lei
Che, Di
Li, Hehong
Gu, Xiaoqiong
The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients
title The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients
title_full The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients
title_fullStr The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients
title_full_unstemmed The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients
title_short The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients
title_sort eif2ak4/rs4594236 ag/gg genotype is a hazard factor of immunoglobulin therapy resistance in southern chinese kawasaki disease patients
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257007/
https://www.ncbi.nlm.nih.gov/pubmed/35812738
http://dx.doi.org/10.3389/fgene.2022.868159
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