Statistical Issues for Genotyping Blood Pressure Sensitivity to Weight Loss and Sodium Diet in the Elderly

• Activity Number: 616
• Type: Contributed
• Date/Time: Thursday, August 2, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Jie Liu*+ and Javier Cabrera and John Kostis and William Kostis
• Companies: Rutgers University and Rutgers University and Robert Wood Johnson Medical School and General Hospital of Boston
• Keywords: Clinical Trials ; Genotype ; Clustering algorithm

Abstract

This work analyzes the Trial of Non-pharmacologic Interventions in the Elderly (TONE),which is a randomized observer blind clinical trial for elderly hypertensives on one or two medications. The patients received intervention in weight reduction, dietary sodium reduction, both weight and sodium reduction, or attention control. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes, or obesity, with the change in blood pressure. We used a recursive partitioning algorithm to select genotypes. Unique binary splitting of observations based on genotypes was chosen such that the increase in the residual sum of squares of models for subgroups was minimized. To test for the difference in effects between the total data set and subgroups, we found the distribution of the difference of the estimates in question due to dependence, used to rank the different genotypes to decide their biological relevance. We found that that patients with certain genotypes treated with weight reduction or sodium reduction had significant different sensitivity from the overall population.