Significant Racial Differences in Thiopurine Methyltransferase Enzyme Activity in a Metropolitan Population

Abstract

Background: Thiopurine methyltransferase (TPMT) is a cytosolic enzyme involved in the metabolism of azathioprine and 6-mercaptopurine. Higher TPMT activity is associated with lower levels of the therapeutic metabolite 6-thioguanine (6-TG). Some therapeutic studies in patients with inflammatory bowel disease have excluded those with intermediate TPMT activity. A small difference in TPMT enzyme activity has been reported between AfricanAmericans and Caucasians. Our own preliminary data suggested that this difference may be more pronounced. We sought to further assess racial differences in TPMT activity to help determine optimal treatment strategies for patients with inflammatory bowel disease. Methods: A retrospective chart review from the electronic medical records of Henry Ford Health System was conducted for patients who had undergone testing for TPMT enzyme activity from June 2004 through September 2010. Testing was performed at Prometheus Laboratories (San Diego, CA). TPMT activity was categorized into low ( 21 EU). Results: 394 patients underwent TPMT testing during the study period. Race was available for 388 patients (246 women and 142 men). The population was composed of 223 Caucasians, 134 African-Americans, and 31 patients of other race. Mean TPMT level was 28.3 EU (SD 9.6) for Caucasians, 23.3 EU(SD 8.2) for African-Americans, and 27.5 EU (SD 9.0) for others (p <0.001). Mean TPMT activity for the 13 Middle Eastern patients in the population was 22.1 (SD 7.8) which was significantly lower than that of Caucasians (p = 0.024). Analysis by TPMT activity category showed that low activity was seen in only 2 patients, and both were Caucasians. Intermediate activity was seen in 37 of the 223 Caucasians (16.6%), 52 of 134 African-Americans (38.8%), and 7 of 31 other race patients (22.6%). Normal TPMT activity was seen for 184 of the 223 Caucasians (82.5%), 82 of the 134 African-Americans (61.2%), and 24 of the 31 patients of other race (77.4%). This distribution was statistically significant (p <0.001). Conclusions: Mean TPMT activity is lower in African-American and Middle Eastern patients compared to Caucasians. African-Americans are more likely to have intermediate TPMT activity compared to Caucasians. Therapeutic studies using 6-mercaptopurine and azathioprine that exclude patients with intermediate TPMT activity may exclude a high proportion of AfricanAmerican patients.