Contribution of the TGFB1 Gene to Myocardial Infarction Susceptibility

Abstract

Carriage frequencies of alleles and genotypes of theTGFB1 gene polymorphous loci –509C>T (rs1800469), 869T>C (rs1982073), 915G>C (rs1800471), which affect the level of cytokine TGF-β1 production, were analyzed in the patients of Russian ethnic descent with myocardial infarction (MI) (406 cases) and in the control group of the same ethnic descent (198 controls). Significant association with MI was observed in carriage frequencies of the alleleTGFB1*–509T (p=0.046, OR =1.45, 95% CI: 1.02-2.06), genotypes TGFB1*869T/T (p=0.0024, OR =1.75, 95% CI: 1.22-2.51), andTGFB1*915G/G (p=0.048, OR=1.76, 95% CI: 1.05-2.97). Linkage disequilibrium analysis for these SNPs has shown that the associations revealed can be considered to be independent. A complex analysis of MI association with combinations of alleles/genotypes of said SNPs indicates their cumulative effect. An analysis of susceptibility to early-onset MI (≤ 50 years old) revealed a positive association of the alleleTGFB1*–509T (p=0.002, OR=2.24, 95% CI: 1.35-3.71) and genotypeTGFB1*869T/T (p=0.008, OR=1.93, 95% CI: 1.18-3.15), as well as their additivity. An analysis of susceptibility to recurrent MI revealed an association of the genotypeTGFB1*–509T/T (p=0.0078, OR=2.60, 95% CI: 1.28-5.28). The results obtained indicate the important role of theTGFB1gene in susceptibility to MI, including early-onset and recurrent MI, in Russians.

Variants of the Coagulation and Inflammation Genes Are Replicably Associated with Myocardial Infarction and Epistatically Interact in Russians

“…This is compelling evidence of validity of these associations, at least for the Russian population. It should be mentioned that earlier we described MI-associated genetic variants TGFB1 rs1982073 [ 24 ] and CRP rs1130864 [ 25 ] in the independent cohort of Moscow patients including individuals with the age at onset of more than 70 years (p f ≤0.05).…”

Association between TGF-β1 -913G/C polymorphism and myocardial infarction risk in a Chinese Han population: a case–control study

“…In addition, they showed -913G/C polymorphism was related to the increased levels of TGF-β1 gene and protein in MI patients [17]. Barsova et al [15] from Russia also explored the association between this SNP and MI risk in a population with 406 cases and 198 controls. They replicated the positive findings of the Iranian study [17], and showed -913G/C polymorphism was a risk factor for MI patients [15].…”

“…Barsova et al [15] from Russia also explored the association between this SNP and MI risk in a population with 406 cases and 198 controls. They replicated the positive findings of the Iranian study [17], and showed -913G/C polymorphism was a risk factor for MI patients [15]. However, Chen et al [23] from England revealed that TGF-β1 -913G/C polymorphism was not the risk of ischemic heart disease and MI in patients with rheumatoid arthritis.…”

“…TGF-β1 -913G/C polymorphism was associated with TGF-β1 protein production in peripheral blood leukocytes [14]. Several studies [15–17] have explored the relationship between TGF-β1 rs1800471 polymorphism and MI risk; however, they yielded conflicting findings. A German study found -913G/C polymorphism was not associated with the risk of MI [16], while other studies showed -913G/C polymorphism was related to increased risk for MI [15,17].…”

“…Several studies [15–17] have explored the relationship between TGF-β1 rs1800471 polymorphism and MI risk; however, they yielded conflicting findings. A German study found -913G/C polymorphism was not associated with the risk of MI [16], while other studies showed -913G/C polymorphism was related to increased risk for MI [15,17]. Up to date, no studies from China investigated the relationship between TGF-β1 -913G/C polymorphism and MI susceptibility.…”