TY - JOUR
T1 - Polymorphisms in the thrombopoietin gene are associated with risk of myocardial infarction at a young age
AU - Webb, Karen E.
AU - Martin, John F.
AU - Hamsten, Anders
AU - Eriksson, Per
AU - Iacoviello, Licia
AU - Gattone, Marinella
AU - Donati, Maria Benedetta
AU - Di Castelnuovo, Augusto
AU - Erusalimsky, Jorge
AU - Humphries, Steve E.
PY - 2001/2/15
Y1 - 2001/2/15
N2 - Five polymorphisms in the thrombopoietin (TPO) gene were identified, one in the 5′ untranslated region (UTR) (C1796T), two within intron 5 (C4830A and A4877C), and two in the 3′ UTR (A5713G and A6160T). The allele frequencies were determined in a group of 450 healthy middle aged men from the UK and found to be 0.46 for 1796T, 0.38 for 4830A, 0.004 for 4877C, 0.47 for 5713G and 0.07 for 6160T. Genotypes for the three common polymorphisms were determined in a group of 176 young male Swedish survivors of a myocardial infarction (MI) and 186 age-matched controls and a group of 156 young Italian survivors of an MI and 147 age and sex matched controls. In both the Swedish and the Italian studies polymorphisms were found to be associated with increased risk of MI. In the Swedish sample the frequency of 4830A was significantly higher in controls (0.40) compared with patients (0.29) (P = 0.003), with an odds ratio for AA homozygotes of 0.48 (0.25-0.92; P = 0.03) compared with CC homozygotes. In the Italian sample the frequency of 5713G was significantly lower in controls (0.31) compared with cases (0.40) (P = 0.03), with an odds ratio for GG homozygotes of 2.29 (1.08-4.89; P = 0.03) compared with AA homozygotes. These risk associations are consistent since 4830A and 5713A show strong allelic association. After adjusting for other measured risk factors the effect on risk was still significant in the Italian sample 2.39 (1.02-5.58), but not in the Swedish sample 0.46 (0.16-1.32). The observation of frequency differences between cases and controls in two independent samples strongly suggests that the TPO gene is involved as a risk factor for developing MI at a young age, but the identified polymorphisms are probably acting as markers for an unidentified functional mutation elsewhere in the gene locus.
AB - Five polymorphisms in the thrombopoietin (TPO) gene were identified, one in the 5′ untranslated region (UTR) (C1796T), two within intron 5 (C4830A and A4877C), and two in the 3′ UTR (A5713G and A6160T). The allele frequencies were determined in a group of 450 healthy middle aged men from the UK and found to be 0.46 for 1796T, 0.38 for 4830A, 0.004 for 4877C, 0.47 for 5713G and 0.07 for 6160T. Genotypes for the three common polymorphisms were determined in a group of 176 young male Swedish survivors of a myocardial infarction (MI) and 186 age-matched controls and a group of 156 young Italian survivors of an MI and 147 age and sex matched controls. In both the Swedish and the Italian studies polymorphisms were found to be associated with increased risk of MI. In the Swedish sample the frequency of 4830A was significantly higher in controls (0.40) compared with patients (0.29) (P = 0.003), with an odds ratio for AA homozygotes of 0.48 (0.25-0.92; P = 0.03) compared with CC homozygotes. In the Italian sample the frequency of 5713G was significantly lower in controls (0.31) compared with cases (0.40) (P = 0.03), with an odds ratio for GG homozygotes of 2.29 (1.08-4.89; P = 0.03) compared with AA homozygotes. These risk associations are consistent since 4830A and 5713A show strong allelic association. After adjusting for other measured risk factors the effect on risk was still significant in the Italian sample 2.39 (1.02-5.58), but not in the Swedish sample 0.46 (0.16-1.32). The observation of frequency differences between cases and controls in two independent samples strongly suggests that the TPO gene is involved as a risk factor for developing MI at a young age, but the identified polymorphisms are probably acting as markers for an unidentified functional mutation elsewhere in the gene locus.
KW - Myocardial infarction
KW - Platelet
KW - Polymorphism
KW - Thrombopoietin
UR - http://www.scopus.com/inward/record.url?scp=0035864611&partnerID=8YFLogxK
U2 - 10.1016/S0021-9150(00)00633-X
DO - 10.1016/S0021-9150(00)00633-X
M3 - Article
C2 - 11257273
AN - SCOPUS:0035864611
SN - 0021-9150
VL - 154
SP - 703
EP - 711
JO - Atherosclerosis
JF - Atherosclerosis
IS - 3
ER -