Publications

BACKGROUND

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. Bridging integrator 1 (BIN1) is a membrane-associated protein important to cardiomyocyte homeostasis and is downregulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing secondary to ARVC.

OBJECTIVE

To determine whether plasma BIN1 levels can be used to measure disease severity in patients with ARVC.

METHODS

We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to correlate with cardiac functional status and predict ventricular arrhythmias.

RESULTS

Mean plasma BIN1 levels were decreased in patients with ARVC with heart failure (15 ± 7 vs 60 ± 17 in patients without heart failure, P <.05; the plasma BIN1 level was 60 ± 10 in non-ARVC normal controls). BIN1 levels correlated inversely with number of previous ventricular arrhythmia (R = -.47; P <.05), and low BIN1 levels correctly classified patients with advanced heart failure or ventricular arrhythmia (receiver operator curve area under the curve of 0.88 ± 0.07). Low BIN1 levels also predicted future ventricular arrhythmias (receiver operator curve area under the curve of 0.89 ± 0.09). In a stratified analysis, BIN1 levels could predict future arrhythmias in patients without severe heart failure (n = 20) with an accuracy of 82%. In the 7 patients with ARVC with serial blood samples, all of whom had evidence of disease progression during follow-up, plasma BIN1 levels decreased significantly (a decrease of 63%; P <.05).

CONCLUSIONS

Plasma BIN1 level seems to correlate with cardiac functional status and the presence or absence of sustained ventricular arrhythmias in a small cohort of patients with ARVC and can predict future ventricular arrhythmias.

BACKGROUND

Extreme hot weather conditions have been associated with increased morbidity and mortality, but risks are not evenly distributed throughout the population. Previously, a heat vulnerability index (HVI) was created to geographically locate populations with increased vulnerability to heat in metropolitan areas throughout the United States.

OBJECTIVES

We sought to determine whether areas with higher heat vulnerability, as characterized by the HVI, experienced higher rates of morbidity and mortality on abnormally hot days.

METHODS

We used Poisson regression to model the interaction of HVI and deviant days (days whose deviation of maximum temperature from the 30-year normal maximum temperature is at or above the 95th percentile) on hospitalization and mortality counts in five states participating in the Environmental Public Health Tracking Network for the years 2000 through 2007.

RESULTS

The HVI was associated with higher hospitalization and mortality rates in all states on both normal days and deviant days. However, associations were significantly stronger (interaction p-value < 0.05) on deviant days for heat-related illness, acute renal failure, electrolyte imbalance, and nephritis in California, heat-related illness in Washington, all-cause mortality in New Mexico, and respiratory hospitalizations in Massachusetts.

CONCLUSION

Our results suggest that the HVI may be a marker of health vulnerability in general, although it may indicate greater vulnerability to heat in some cases.

PURPOSE

Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome.

PATIENTS AND METHODS

We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials.

RESULTS

Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10(-20) in whites; P = 1 × 10(-6) in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10(-8)). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics.

CONCLUSION

ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.