Abstract
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.
Keywords
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Article info
Publication history
Accepted:
August 21,
2000
Received in revised form:
August 11,
2000
Received:
April 20,
2000
Identification
Copyright
© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
