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Transforming growth factor-beta gene polymorphisms and coronary artery disease

Syrris, P; Carter, ND; Metcalfe, JC; Kemp, PR; Grainger, DJ; Kaski, JC; Crossman, DC; ... Heathcote, K; + view all (1998) Transforming growth factor-beta gene polymorphisms and coronary artery disease. CLIN SCI , 95 (6) 659 - 667.

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1 Transforming growth factor-beta 1 is a cytokine with a very wide spectrum of biological activities. Previous studies have shown that it is involved in a number of physiological and pathological processes including heart disease. in our study we aimed to scan the transforming growth factor-beta 1 locus for polymorphisms and to identify haplotypes significantly associated with a predisposition to coronary atherosclerosis.2. Two patient groups comprising 244 angiographically normal individuals and 655 patients with coronary artery disease were recruited from London and Sheffield. DNA samples from these subjects were screened for mutations in the transforming growth factor-beta 1 locus and all subjects were genotyped by a coupled polymerase chain reaction-restriction enzyme digestion method.3. Five polymorphisms have been identified in the transforming growth factor-beta 1 gene at positions G-800A, C-509T in the promoter region, Leu(10) --> Pro, Arg(25) --> Pro in exon 1 and Thr(263) --> Ile in exon 5. No significant difference in frequencies for any of the five polymorphisms was found between controls and patients with coronary artery disease. Similarly, there was no correlation between these polymorphisms and hypertension.4. The genotypes of all the individuals participating in the study were assigned to seven main haplotypes of the transforming growth factor-beta 1 locus, Based on species comparison data we propose that GCCGC is the ancestral haplotype in humans.5. Our data suggest that these transforming growth factor-beta 1 polymorphisms are not associated with coronary artery disease and therefore their presence alone would not be a genetic risk factor for predisposition to coronary artery disease.

Type: Article
Title: Transforming growth factor-beta gene polymorphisms and coronary artery disease
Keywords: coronary artery disease, haplotypes, human transforming growth factor-beta 1, polymorphisms, CELL SUPPRESSOR FACTOR, EXTRACELLULAR-MATRIX, COMPLEMENTARY-DNA, ENDOTHELIAL-CELLS, TGF-BETA, EXPRESSION, FACTOR-BETA-1, SEQUENCE, GROWTH-FACTOR-BETA-1, ACTIVATION
URI: http://discovery.ucl.ac.uk/id/eprint/129764
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