Marlene S Williams1, Lisa Yanek2, Roy C Ziegelstein2, Una McCann3, Nauder Faraday4. 1. Division of Cardiology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, United States of America. Electronic address: mwillia1@jhmi.edu. 2. Division of Cardiology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, United States of America. 3. Department of Psychiatry, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, United States of America. 4. Department of Anesthesia, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, United States of America.
Abstract
INTRODUCTION: Genetic differences between races have been hypothesized to contribute to differences in outcome from acute coronary syndromes (ACS). Our objective was to assess racial differences in genetic variations in the platelet serotonin transporter (5HTT) and receptor in patients with ACS. MATERIALS AND METHODS: 127 consecutive patients, African Americans (AA) = 27; Caucasian (C) =100, admitted with ACS were evaluated for platelet function by serotonin (5HT) induced platelet activation. All patients were genotyped for two polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) S/L and LG/LA and one polymorphism of the serotonin 2A receptor (5-HT2A, T102C) gene. All patients were followed for major and minor adverse cardiac events at 12 months. RESULTS: AA when compared to C had a lower prevalence of the HTTLPR S allele (21% vs 45%, p = 0.0003) and a higher prevalence of the LG allele (24% vs 4.5%, p = 0.0001). Allelic frequency of the 5-HT2A T102C allele was not significantly different between the races. Platelet activation was lower in AA compared to C, median EC50 5HT was 12.08 μg vs 2.14 μg (p = 0.001). The 5-HTTLPR and the 5-HT2A polymorphisms were not associated with platelet functional responses to serotonin. There were no significant differences in major or minor adverse cardiac events in patients with serotonin transporter or receptor polymorphisms. CONCLUSION: We found a lower prevalence of the S allele and a higher prevalence of the G allele in AA with ACS. We also found decreased platelet activation in AA which did not correlate with serotonin-related platelet polymorphisms. It is unclear if other contributing factors may explain these platelet functional differences.
INTRODUCTION: Genetic differences between races have been hypothesized to contribute to differences in outcome from acute coronary syndromes (ACS). Our objective was to assess racial differences in genetic variations in the platelet serotonin transporter (5HTT) and receptor in patients with ACS. MATERIALS AND METHODS: 127 consecutive patients, African Americans (AA) = 27; Caucasian (C) =100, admitted with ACS were evaluated for platelet function by serotonin (5HT) induced platelet activation. All patients were genotyped for two polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) S/L and LG/LA and one polymorphism of the serotonin 2A receptor (5-HT2A, T102C) gene. All patients were followed for major and minor adverse cardiac events at 12 months. RESULTS: AA when compared to C had a lower prevalence of the HTTLPR S allele (21% vs 45%, p = 0.0003) and a higher prevalence of the LG allele (24% vs 4.5%, p = 0.0001). Allelic frequency of the 5-HT2A T102C allele was not significantly different between the races. Platelet activation was lower in AA compared to C, median EC50 5HT was 12.08 μg vs 2.14 μg (p = 0.001). The 5-HTTLPR and the 5-HT2A polymorphisms were not associated with platelet functional responses to serotonin. There were no significant differences in major or minor adverse cardiac events in patients with serotonin transporter or receptor polymorphisms. CONCLUSION: We found a lower prevalence of the S allele and a higher prevalence of the G allele in AA with ACS. We also found decreased platelet activation in AA which did not correlate with serotonin-related platelet polymorphisms. It is unclear if other contributing factors may explain these platelet functional differences.
Authors: Shanthi Mendis; Kristian Thygesen; Kari Kuulasmaa; Simona Giampaoli; Markku Mähönen; Kathleen Ngu Blackett; Liu Lisheng Journal: Int J Epidemiol Date: 2010-10-05 Impact factor: 7.196
Authors: Leonard C Edelstein; Lukas M Simon; Raúl Teruel Montoya; Michael Holinstat; Edward S Chen; Angela Bergeron; Xianguo Kong; Srikanth Nagalla; Narla Mohandas; David E Cohen; Jing-fei Dong; Chad Shaw; Paul F Bray Journal: Nat Med Date: 2013-11-10 Impact factor: 53.440