One Size Does Not Fit All

Portman, Michael A.; Shrestha, Sadeep

doi:10.1161/circgenetics.117.001917

Cited by 6 publications

(1 citation statement)

References 18 publications

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“…20,21 Thus, no universal biomarker or algorithm accurately predicts risk for persistent CAA in North America. 22 Currently available data indicate that KD susceptibility and treatment response depend on an individual patient's genetic background. [23][24][25][26][27][28][29][30][31] Discrepancies among races or ethnicities also…”

Section: I S C L a I M E R : T H E M A N U S C R I P T A N D I T S C ...mentioning

confidence: 99%

Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease

Shrestha,

Wiener,

Chowdhury

et al. 2024

Preprint

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BackgroundKawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The pathological walls of afflicted coronary arteries show propensity for forming thrombosis and aneurysms. The mechanism of coronary artery aneurysms (CAA) despite intravenous gamma globulin (IVIG) treatment is not known.MethodsWe performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z>2.5 and large coronary aneurysm (CAA/L) (N = 92) as z>5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. We performed functional mapping and annotation (FUMA) analysis and further assessed the predictive risk score of genomic risk loci using the area under the receiver operating characteristic curve (AUC).ResultsThe top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p<6.32E-08 most significant). Variants inSMAT4, LOC100127,PTPRD, TCAF2andKLRC2were the most significant non-intergenic SNPs. FUMA identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of theseNDUFA5has been implicated in KD CAA andMICUandZMAT4has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an AUC of 0.86.ConclusionsThis pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD patients. We have identified multiple novel SNPs associated with CAA/L and related genes with potential functional implications. The study shows that genomics can help define the cause of CAA/L to guide management and improve risk stratification of KD patients.

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Section: I S C L a I M E R : T H E M A N U S C R I P T A N D I T S C ...mentioning

confidence: 99%

Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease

Shrestha,

Wiener,

Chowdhury

et al. 2024

Preprint

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Kawasaki Disease and Clinical Outcome Disparities Among Black Children

Padilla

Collins

Idigo

et al. 2021

The Journal of Pediatrics

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Study design ICD codes were used to identify children with Kawasaki disease admitted to a tertiary Southeast U.S. center. Subjects diagnosed and treated according to AHA criteria were included. Demographic, laboratory, clinical and echocardiographic data from EMR (2000-2015) were compared between Blacks and Whites. Results Data from 369 subjects (52% Whites and 48% Blacks) were included in our analysis. No significant differences related to timely admission, IVIG treatment or, coronary artery abnormalities during hospitalization were observed, Blacks showed lower IVIG response rates for those administered IVIG within 10 days of fever onset (86.6% vs 95.6%, P = 0.007). Blacks received more ancillary drugs (9.6% vs 2.6%, P value 0.003), and endured longer hospitalizations (5±3.9 v s 3.4±2.2 days, P = 0.001). Blacks presented with higher C-reactive protein, erythrocyte sedimentation rate and; lower hemoglobin, albumin and, sodium. Blacks showed a greater proportion of persistent coronary artery abnormalities at follow-up when compared with Whites (14.5% vs 6.3%, P = .03, second follow-up ECHO; 21.2% vs 6.9%, P = 0.01 third follow-up ECHO). Conclusion Black children with Kawasaki disease had higher IVIG refractory prevalence, severe inflammation, received more ancillary treatments and, longer hospitalizations than White children. Despite no racial differences in time to diagnosis or initial treatment, there was higher coronary artery abnormality persistence among Black children at follow-up.

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Padilla

Portman

Shrestha

2021

The Journal of Pediatrics

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Rash was identified less frequently in black children in the study. 1 Research shows erythema migrans is identified less often in black individuals, leading to a higher incidence of late stage Lyme disease presentations. 5,6 Racial bias in medical resources and education means that dermatologic conditions are less likely to be identified on black skin, further exacerbating health disparities. 7 It is important to acknowledge the possible impacts of this phenomenon in Kawasaki disease.Although genetics have been shown to play a role in some individuals' susceptibility to Kawasaki disease, the cause of Kawasaki disease remains unknown and genetics do not explain all cases. 8 Further, the scientific literature continues to show that race cannot be used as a proxy for genetics. 9,10 Thus, the authors' recommendation to include race in treatment algorithms for Kawasaki disease warrants caution. The use of race in diagnostic or therapeutic decision making can exacerbate disparities by providing different care based on race. 11 Racial and ethnic disparities are not intrinsic to the individual's biology, but rather the systemic inequity and racism that plagues our society.

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One Size Does Not Fit All

Cited by 6 publications

References 18 publications

Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease

Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease

Kawasaki Disease and Clinical Outcome Disparities Among Black Children

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