Undiagnosed Pediatric Elevated Blood Pressure Is Characterized by Induction of Proinflammatory and Cytotoxic Mediators

Figures

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  Figure 1.. Study design. Evaluation of immune gene expression in relation to systolic and diastolic blood pressure was performed in the 15-years follow-up of the GINIplus study (The German Infant Study on the Influence of Nutrition Intervention plus Air pollution and Genetics on Allergy Development; discovery cohort). Identified candidate genes, which were associated to BP, were subsequently analyzed in the 15-years follow-up of the LISA study (Influences of Lifestyle-related factors on the Immune System and the Development of Allergies in Childhood; validation cohort).

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  Figure 2.. Immune gene expression in adolescents with elevated blood pressure (BP). A, Forest plots indicate associated risk for elevated systolic BP (eSBP) and elevated diastolic BP (eDBP) of those immune genes, which were significantly associated with BP in the discovery cohort (n=877 controls, n=98 eDBP, n=171 eSBP) as determined by adjusted logistic regression. B, Risk increase for elevated BP of significantly associated genes identified in the discovery cohort was assessed in the validation cohort (n=529 controls, n=88 eDBP, n=133 eSBP). Odds ratio (#OR) from logistic regression adjusted for sex, body mass index (BMI), parental hypertension (HTN), parental education, season of BP measurement and study center. *Significant association with P<0.05. C, Risk factors associated with HTN in adolescents. Shown are ORs from univariate logistic regression for the discovery cohort in black (n=877 controls, n=225 HTN class), and in blue for the validation cohort (n=529 controls, n=179 HTN class). IFNG indicates interferon gamma; and TF, transcription factor.

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  Figure 3.. Influence of body mass index (BMI) on IL1B (interleukin 1B) expression and elevated systolic blood pressure (eSBP) in adolescents. A, Overlap of genes significantly associated to eSBP (refer to Figure 2) and with BMI as determined by multiple regression analysis (see Table S9 for multiple regression results). B, Mediation analysis for the relationship of BMI, IL1B transcription, and eSBP in the GINIplus (The German Infant Study on the Influence of Nutrition Intervention Plus Air Pollution and Genetics on Allergy Development) discovery cohort (n=1044, black font) and the LISA (Influences of Lifestyle-related factors on the Immune System and the Development of Allergies in Childhood) validation cohort (n=661, blue font), respectively. Model was adjusted for sex, parental hypertension (HTN), parental education, season of BP measurement and study center. Effect sizes for the indirect paths are given as β values with +/−95% CIs. Significance determined by bias-corrected bootstrapping. FOS indicates Fos proto-oncogene; and and IL2RB, interleukin 2 receptor beta.