Association between the M235T polymorphism of the AGT gene and cytokines in patients with hypertension

Abstract

Abstract. The aim of the present study was to explore the association between the M235T polymorphism of the angiotensinogen (AGT) gene and cytokines in patients with essential hypertension (EH). A total of 300 patients with EH and an agematched control group of 150 individuals without EH, secondary hypertension, myocardial infarction and diabetes were enrolled in this study. Polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP) was used to detect variation in the target genotype, and enzyme-linked immunosorbant assay (ELISA) was used to detect the cytokine [interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)] concentrations. The AGT gene 235T allele and 235TT genotype frequencies in hypertensive patients were slightly higher than those in the controls. Furthermore, in the hypertensive subjects with the AGT gene 235T allele, the concentrations of IL-1 and TNF-α were significant higher than those in the controls. The results from our study suggest that the higher AGT gene TT genotype and 235T allele frequencies may be risk factors for hypertension. High frequencies of the AGT gene 235T allele and high cytokine concentrations (IL-1 and TNF-α) may promote the transcription and expression of AGT, particularly in hypertensive patients with the 235TT genotype. IntroductionHypertension has been recognized as a significant risk factor for the development of cardiovascular diseases, including coronary heart disease (CHD), myocardial infarction (MI) and stroke, all of which are principal causes of cardiovascular morbidity and mortality in humans. Essential hypertension (EH) is a complex, polygenic disease in which numerous genes control the blood pressure level. Several candidate genes, all selected from the renin-angiotensin system-related genes, have been examined. One of the candidate genes is the gene encoding angiotensinogen (AGT), the precursor of the vasoactive peptide, angiotensin II. The angiotensin I-converting enzyme (ACE) gene has also been associated with EH in the majority of the population. In recent years, the correlation between the molecular variant of the AGT gene, M235T, and EH has started to receive attention (1-6). AGT in the circulation is mainly synthesized in the liver. The plasma AGT level mainly reflects this synthesis. It has been discovered that the expression of the AGT gene in the liver is regulated by certain cytokines. It has been reported that these cytokines [interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)] are likely to be the main activation factors in AGT gene expression. They activate the expression of the AGT gene, elevate the concentrations of AGT and ultimately accelerate the development of hypertension. In addition, IL-1 and TNF-α also induce proliferation of the smooth muscle blood vessel cells and arteriosclerosis. Studies on the association between the M235T polymorphism of the AGT gene and cytokines in hypertensive Chinese patients have been rarely reported. The aim of this study was to analyze the M235T polymorphism ...

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Increased Plasma Angiotensinogen Level, BMI and Its Association with the Angiotensinogen Gene M235T Polymorphism and Essential Hypertension in Myanmar

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