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

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 may be involved in cardiovascular physiopathology. In the present study, we assessed whether the TGF-beta 1 gene is a candidate gene for coronary heart disease or hypertension. We screened the coding region and 2181 bp upstream of the TGF-beta 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-beta 1 polymorphisms in 563 patients with myocardial infarction and 629 control subjects from four regions in Northern Ireland and France. The Pro25 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 angiographically assessed coronary artery disease in patients. The presence of a Pro25 allele 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 Pro25 than in hormozygotes for Arg25 (odds ratio, 0.43, 95% confidence interval, 0.19 to 0.92; P < .03). Since the Pro25 allele 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.

TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

“…Several functional single nucleotide polymorphisms (SNPs) within the TGF-␤1 gene have been identified including CϪ509T, codon 10 (T ϩ 29C), and codon 25 (G ϩ 74C) (10). The variant alleles of CϪ509T and codon 10 are associated with higher TGF-␤1 protein levels in serum.…”

TGF-β1 polymorphisms and arterial stiffness; the Rotterdam Study

“…There are several commonly known (potentially) functional polymorphisms in this gene. Cambien et al 23 described the À988 C/A, À800 G/A, À509 C/T polymorphisms (promoter region); a Cinsertion at position þ 72 (non-translated region); and in addition codons 10 Leu/Pro (c10) and 25 Arg/ Pro (c25) (signal peptide sequence) and 263 Thr/Ile (c263) (precursor part of the protein). Of these, þ 72 was in almost complete linkage disequilibrium with c25, whereas -988 C/A was extremely rare.…”

“…Of these, þ 72 was in almost complete linkage disequilibrium with c25, whereas -988 C/A was extremely rare. 23 Grainger et al 24 described the -509 C/T polymorphism to be associated with levels of TGF-b1.…”

“…[23][24][25] The c10 and c25 polymorphisms are located in the signal peptide sequence, which is involved in export of synthesized proteins across membranes of the endoplasmatic reticulum, thereby possibly influencing TGF-b levels. 23 The c10 and c25 polymorphisms are also located at potentially important positions that influence activation of the TGF-b protein. 25 To the best of our knowledge, these (potentially) functional polymorphisms have not been investigated in association with arterial stiffness before.…”

TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases

“…Two single-nucleotide polymorphisms (SNPs) at positions þ 869 (T-C) and þ 915 (G-C) in the signal protein sequence, which change codon 10 (Leu-Pro) and codon 25 (Arg-Pro), respectively, have been related to variations in the production of TGF-b1, both in vitro and at the serum level. 18,19 The correlation between these polymorphisms and disease status has been studied in a diverse range of diseases, [20][21][22][23] but no studies have been published that examine the possible link between TGFB1 gene polymorphisms and H. pylori-related diseases. Therefore, the aim of our study was to assess whether the TGFB1 T þ 869C and TGFB1 G þ 915C polymorphisms are involved in susceptibility to and clinical characteristics of PU and GC.…”