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The prevalence of the prothrombin gene variant C20209T in African-Americans and Caucasians and lack of association with venous thromboembolism
Thrombosis Research (2006) 118, 767 — 768
intl.elsevierhealth.com/journals/thre
Letter to the Editors-in-Chief The prevalence of the prothrombin gene variant C20209T in African-Americans and Caucasians and lack of association with venous thromboembolism Dear Sir, The prothrombin G20210A gene variant found in the 3V-untranslated region has been found to be a moderate genetic risk factor for venous thromboembolism (VTE) [1,2]. Similar to FV Leiden, this variant varies among populations with a reported prevalence ranging from 1% to 4% in Caucasians [1— 3]. It is rare both in African-Americans and West Africans [4,5]. Recently Warshawsky et al. [3] reported a new prothrombin gene variant, C20209T, which appeared to be confined to African-Americans. To expand these findings and to determine its relationship to VTE in African-Americans, we utilized an ongoing case-control study of risk factors for VTE in African-Americans and Caucasians. The Genetic Attributes and Thrombosis Epidemiology (GATE) study was approved by the Human Investigations Committee of Emory University and the Institutional Review Board at the Centers for Disease Control and Prevention [6]. Potential case subjects from two university-owned hospitals between the ages of 18 and 70 were identified from a daily review of medical charts of all patients receiving unfractioned or low-molecular weight heparin. The VTE events were objectively confirmed. In the initial report, the average age of both cases and controls were 49 years and the cases were more likely to have a family history of VTE as compared to the controls. A history of cancer was more prevalent among Caucasian cases while kidney disease, hypertension and diabetes were more common in African-Americans. The prothrombin G20210A gene variant was not associated with VTE in African-Americans and the 20210A allele was absent in the African-American controls. Likewise and in contrast to Caucasians, factor V Leiden was not associated with VTE in AfricanAmericans [6]. 0049-3848/$ - see front matter. Published by Elsevier Ltd. doi:10.1016/j.thromres.2005.12.001
The present analysis includes 301 African-American cases and 270 African-American controls as well as 323 Caucasian cases and 344 Caucasian controls. Two (0.7%) African-American controls and 4 (1.3%) African-American cases were heterozygous for C20209T (no subject in the study was homozygous for the C20209T mutation). However, this difference is not statistically significant ( P N 0.20). Among Caucasians, only one control was heterozygous for C20209T. The prevalence of the C20209T allele variant was statistically significantly higher among African-Americans than Caucasians (twotailed, exact P value = 0.047 among all subjects). In comparison, the prevalence of the G20210A variant was 1.3% in the African-American cases and the variant allele was not present in the African-American control group. In summary, our findings support those of Warshawsky et al. [3] in that the prothrombin C20209T variant is more common among AfricanAmericans than it is among Caucasians. We found no association between VTE and the C20209T variant. However, since the variant is rare both among African-Americans and Caucasians, even this relatively large study had little statistical power.
References [1] Poort RS, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3V-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698 – 703. [2] Leroyer C, Mercier B, Oger E, Chenu E, Abgrall J-F, Ferec C, et al. Prevalence of 20210A allele of the prothrombin gene in venous thromboembolism patients . Thromb Haemost 1998;80:49 – 51. [3] Warshawsky I, Hren C, Sercia L, Shadrach B, Deithcher SR, Newton E, et al. Detection of a novel point mutation of the prothrombin gene at position 20209. Diagn Mol Pathol 2002;11:152 – 6. [4] Dilley A, Austin H, Hooper WC, El-Jamil M, Whitsett C, Wenger NK, et al. Prevalence of the prothrombin 20210 G-toA variant in blacks: infants, patients with venous thrombosis, patients with myocardial infarction, and control subjects. J Lab Clin Med 1998;132:452 – 5.
768 [5] Rahimy MC, Krishnamoorthy R, Ahouignan G, Laffan M, Vulliamy T. The 20210A allele of prothrombin is not found among sickle cell disease patients from West Africa. Thromb Haemost 1998;79:444. [6] Dowling NF, Austin H, Dilley A, Whitsett C, Evatt BL, Hooper WC. The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE study. J Thromb Haemost 2003;1:80 – 7.
W. Craig Hooper Hereditary Blood Disorders, National Centers for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, MS DO2, 1600 Clifton Rd, Atlanta GA, United States E-mail address: [email protected]. Corresponding author. Tel.: +1 404 639 3750. Stacy Roberts Nicole Dowling Hereditary Blood Disorders, National Centers for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, MS DO2, 1600 Clifton Rd, Atlanta GA, United States
Letter to the Editors-in-Chief Harland Austin Cathy Lally Rollins School of Public Health, Emory University, Atlanta GA, United States Carolyn Whitsett Department of Pathology, Mt. Sinai School of Medicine, New York, NY, United States 6 June 2005
intl.elsevierhealth.com/journals/thre
Letter to the Editors-in-Chief The prevalence of the prothrombin gene variant C20209T in African-Americans and Caucasians and lack of association with venous thromboembolism Dear Sir, The prothrombin G20210A gene variant found in the 3V-untranslated region has been found to be a moderate genetic risk factor for venous thromboembolism (VTE) [1,2]. Similar to FV Leiden, this variant varies among populations with a reported prevalence ranging from 1% to 4% in Caucasians [1— 3]. It is rare both in African-Americans and West Africans [4,5]. Recently Warshawsky et al. [3] reported a new prothrombin gene variant, C20209T, which appeared to be confined to African-Americans. To expand these findings and to determine its relationship to VTE in African-Americans, we utilized an ongoing case-control study of risk factors for VTE in African-Americans and Caucasians. The Genetic Attributes and Thrombosis Epidemiology (GATE) study was approved by the Human Investigations Committee of Emory University and the Institutional Review Board at the Centers for Disease Control and Prevention [6]. Potential case subjects from two university-owned hospitals between the ages of 18 and 70 were identified from a daily review of medical charts of all patients receiving unfractioned or low-molecular weight heparin. The VTE events were objectively confirmed. In the initial report, the average age of both cases and controls were 49 years and the cases were more likely to have a family history of VTE as compared to the controls. A history of cancer was more prevalent among Caucasian cases while kidney disease, hypertension and diabetes were more common in African-Americans. The prothrombin G20210A gene variant was not associated with VTE in African-Americans and the 20210A allele was absent in the African-American controls. Likewise and in contrast to Caucasians, factor V Leiden was not associated with VTE in AfricanAmericans [6]. 0049-3848/$ - see front matter. Published by Elsevier Ltd. doi:10.1016/j.thromres.2005.12.001
The present analysis includes 301 African-American cases and 270 African-American controls as well as 323 Caucasian cases and 344 Caucasian controls. Two (0.7%) African-American controls and 4 (1.3%) African-American cases were heterozygous for C20209T (no subject in the study was homozygous for the C20209T mutation). However, this difference is not statistically significant ( P N 0.20). Among Caucasians, only one control was heterozygous for C20209T. The prevalence of the C20209T allele variant was statistically significantly higher among African-Americans than Caucasians (twotailed, exact P value = 0.047 among all subjects). In comparison, the prevalence of the G20210A variant was 1.3% in the African-American cases and the variant allele was not present in the African-American control group. In summary, our findings support those of Warshawsky et al. [3] in that the prothrombin C20209T variant is more common among AfricanAmericans than it is among Caucasians. We found no association between VTE and the C20209T variant. However, since the variant is rare both among African-Americans and Caucasians, even this relatively large study had little statistical power.
References [1] Poort RS, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3V-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698 – 703. [2] Leroyer C, Mercier B, Oger E, Chenu E, Abgrall J-F, Ferec C, et al. Prevalence of 20210A allele of the prothrombin gene in venous thromboembolism patients . Thromb Haemost 1998;80:49 – 51. [3] Warshawsky I, Hren C, Sercia L, Shadrach B, Deithcher SR, Newton E, et al. Detection of a novel point mutation of the prothrombin gene at position 20209. Diagn Mol Pathol 2002;11:152 – 6. [4] Dilley A, Austin H, Hooper WC, El-Jamil M, Whitsett C, Wenger NK, et al. Prevalence of the prothrombin 20210 G-toA variant in blacks: infants, patients with venous thrombosis, patients with myocardial infarction, and control subjects. J Lab Clin Med 1998;132:452 – 5.
768 [5] Rahimy MC, Krishnamoorthy R, Ahouignan G, Laffan M, Vulliamy T. The 20210A allele of prothrombin is not found among sickle cell disease patients from West Africa. Thromb Haemost 1998;79:444. [6] Dowling NF, Austin H, Dilley A, Whitsett C, Evatt BL, Hooper WC. The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE study. J Thromb Haemost 2003;1:80 – 7.
W. Craig Hooper Hereditary Blood Disorders, National Centers for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, MS DO2, 1600 Clifton Rd, Atlanta GA, United States E-mail address: [email protected]. Corresponding author. Tel.: +1 404 639 3750. Stacy Roberts Nicole Dowling Hereditary Blood Disorders, National Centers for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, MS DO2, 1600 Clifton Rd, Atlanta GA, United States
Letter to the Editors-in-Chief Harland Austin Cathy Lally Rollins School of Public Health, Emory University, Atlanta GA, United States Carolyn Whitsett Department of Pathology, Mt. Sinai School of Medicine, New York, NY, United States 6 June 2005