Polymorphisms of the Transforming Growth Factor-β1 Gene in Relation to Myocardial Infarction and Blood Pressure

Abstract

Transforming growth factor-β1 (TGF-β1) plays an important role in the modulation of cellular growth and differentiation and the production and degradation of the extracellular matrix. A number of experimental results suggest that TGF-β1 may be involved in cardiovascular physiopathology. In the present study, we assessed whether the TGF-β1 gene is a candidate gene for coronary heart disease or hypertension. We screened the coding region and 2181 bp upstream of the TGF-β gene for polymorphisms and identified seven polymorphisms: 3 in the upstream region of the gene at positions −988, −800, and −509 from the first transcribed nucleotide; 1 in a nontranslated region at position +72; 2 in the signal peptide sequence Leu¹⁰→Pro, Arg²⁵→Pro; and 1 in the region of the gene coding for the precursor part of the protein not present in the active form, Thr²⁶³→Ile. We analyzed these TGF-β1 polymorphisms in 563 patients with myocardial infarction and 629 control subjects from four regions in Northern Ireland and France. The Pro²⁵allele was more frequent in patients than in control subjects in Belfast (P<.01) and Strasbourg (P<.05). The TGF-β1 polymorphisms were not associated with the degree of angiographically assessed coronary artery disease in patients. The presence of a Pro²⁵allele was associated with a lower systolic pressure in the four control groups (P<.002), and a history of hypertension was significantly less frequent in homozygotes or heterozygotes for Pro²⁵than in homozygotes for Arg²⁵(odds ratio, 0.43; 95% confidence interval, 0.19 to 0.92;P<.03). Since the Pro²⁵allele was associated with an increased risk of myocardial infarction and a reduced risk of hypertension, we favor a cautious interpretation of these apparently inconsistent results. Other studies will need to verify whether these associations are real.