POLYMORPHISMS OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 GENE IN RELATION TO MYOCARDIAL-INFARCTION AND BLOOD-PRESSURE - THE ETUDE-CAS-TEMOIN-DE-LINFARCTUS-DU-MYOCARDE (ECTIM) STUDY

Transforming growth factor-beta 1 (TGF-beta 1) plays an important role in the modulation of cellular growth and differentiation and the prod uction and degradation of the extracellular matrix. A number of experi mental results suggest that TGF-beta 1 may be involved in cardiovascul ar physiopathology. In the present study, we assessed whether the TGF- beta 1 gene is a candidate gene for coronary heart disease or hyperten sion. We screened the coding region and 2181 bp upstream of the TGF-be ta gene for polymorphisms and identified seven polymorphisms: 3 in the upstream region of the gene at positions -988, -800, and -509 from th e first transcribed nucleotide; 1 in a nontranslated region at positio n +72; 2 in the signal peptide sequence Leu(10)-->Pro, Arg(25)-->Pro; and 1 in the region of the gene coding for the precursor part of the p rotein not present in the active form, Thr(263)-->Ile. We analyzed the se TGF-beta 1 polymorphisms in 563 patients with myocardial infarction and 629 control subjects from four regions in Northern Ireland and Fr ance. The pro(25) allele was more frequent in patients than in control subjects in Belfast (P < .01) and Strasbourg (P < .05). The TGF-beta 1 polymorphisms were not associated with the degree of angiographicall y assessed coronary artery disease in patients. The presence of a Pro( 25) allele was associated with a lower systolic pressure in the four c ontrol groups (P < .002), and a history of hypertension was significan tly less frequent in homozygotes or heterozygores for pro(25) than in homozygotes for Arg(25) (odds ratio, 0.43; 95% confidence interval, 0. 19 to 0.92; P < .03). Since the pro(25) allele was associated with an increased risk of myocardial infarction and a reduced risk of hyperten sion, we favor a cautious interpretation of these apparently inconsist ent results. Other studies will need to verify whether these associati ons are real.