Contribution of the TGFB1 Gene to Myocardial Infarction Susceptibility

Abstract

Carriage frequencies of alleles and genotypes of the TGFB1 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 allele TGFB1*-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), and TGFB1*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 allele TGFB1*-509T (p=0.002, OR=2.24, 95% CI: 1.35-3.71) and genotype TGFB1*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 genotype TGFB1*-509T/ T (p=0.0078, OR=2.60, 95% CI: 1.28-5.28). The results obtained indicate the important role of the TGFB1 gene in susceptibility to MI, including early-onset and recurrent MI, in Russians. KEYWORDS myocardial infarction; Russians; genes; allelic polymorphism; transforming growth factor β1; TGFB1; APSampler. ABBREVIATIONS dNTP -deoxynucleoside triphosphate; LD -linkage disequilibrium; SD -standard deviation; SNP -single nucleotide polymorphism; TGF-β1 -transforming growth factor beta 1; TGFB1 -gene encoding transforming growth factor beta 1; CI -confidence interval; IHD -ischemic heart disease; MI -myocardial infarction; OR -odds ratio; PCR -polymerase chain reaction; PCR-SSP -polymerase chain reaction with sequence-specific primers; CVD -cardiovascular diseases.

Analysis of the Association between the <i>Tgfb1</i> Gene Haplotype and Liver Diseases in Children

“…The frequencies of SNPs rs1800469, rs1800470, and rs1800471 in healthy individuals identified in our study are consistent with the data of other domestic authors [ 17 , 18 ]. A comparison of the distribution of the allele frequencies studied in our work with the data deposited into the U.S. National Center for Biotechnology Information (NCBI) also did not reveal significant differences from that of Tgfb1 in the European population: rs1800469 – A(37%)/G(63%); rs1800470 – A(56%)/G(44%); and rs1800471 – C(94%)/G(6%).…”

“…The prevalence of the three most common haplotypes did not vary significantly between patients and healthy individuals. The analysis of the same Tgfb1 haplotypes conducted by other authors showed a similar prevalence of the most common haplotype, G-A-C, in healthy individuals, which was about 50–60% [ 17 , 20 ].…”

Вклад Трансформирующего Фактора Роста Β1, Эндотелина-1, Коллагена IV Типа Иполиморфизмов Их Генов В Ремоделирование Артерий

“…Цитокин TФРβ1 кодируется геном TФРβ1 (OMIM 190180), который расположен на длинном плече 19-й хромосомы в локусе 19q13.2 и состоит из 7 экзонов, разделенных 6 интронами. В настоящее время установлен ряд важных полиморфизмов -rs1800469, rs1800470, rs1800471, rs1800473 [33]. Полиморфизм rs1800469 локализован в промотерной области гена, Т-вариант полиморфизма приводит к повышению концентрации TФРβ1.…”