Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified from Genome-Wide Association Study in Kawasaki Disease

Ho Chang Kuo, Henry Sung Ching Wong, Wei Pin Chang, Ben Kuen Chen, Mei Shin Wu, Kuender D. Yang, Kai Sheng Hsieh, Yu Wen Hsu, Shih Feng Liu, Xiao Liu, Wei Chiao Chang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background - Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. Methods and Results - To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10-03 and 8.224×10-10, respectively). Conclusions - This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.

Original languageEnglish
Article numbere001625
JournalCirculation: Cardiovascular Genetics
Volume10
Issue number5
DOIs
Publication statusPublished - Oct 1 2017

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Mucocutaneous Lymph Node Syndrome
Genome-Wide Association Study
Intravenous Immunoglobulins
Single Nucleotide Polymorphism
Alleles
Genetic Markers
Fever
Odds Ratio

Keywords

  • alleles
  • genetics
  • genome-wide association study
  • odds ratio
  • pharmacogenetics

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified from Genome-Wide Association Study in Kawasaki Disease. / Kuo, Ho Chang; Wong, Henry Sung Ching; Chang, Wei Pin; Chen, Ben Kuen; Wu, Mei Shin; Yang, Kuender D.; Hsieh, Kai Sheng; Hsu, Yu Wen; Liu, Shih Feng; Liu, Xiao; Chang, Wei Chiao.

In: Circulation: Cardiovascular Genetics, Vol. 10, No. 5, e001625, 01.10.2017.

Research output: Contribution to journalArticle

Kuo, Ho Chang ; Wong, Henry Sung Ching ; Chang, Wei Pin ; Chen, Ben Kuen ; Wu, Mei Shin ; Yang, Kuender D. ; Hsieh, Kai Sheng ; Hsu, Yu Wen ; Liu, Shih Feng ; Liu, Xiao ; Chang, Wei Chiao. / Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified from Genome-Wide Association Study in Kawasaki Disease. In: Circulation: Cardiovascular Genetics. 2017 ; Vol. 10, No. 5.
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abstract = "Background - Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. Methods and Results - To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10-03 and 8.224×10-10, respectively). Conclusions - This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.",
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AB - Background - Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. Methods and Results - To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10-03 and 8.224×10-10, respectively). Conclusions - This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.

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