Stromelysin-1 and Interleukin-6 Gene Promoter Polymorphisms Are Determinants of Asymptomatic Carotid Artery Atherosclerosis

Abstract

Abstract-The functional 5A/6A polymorphism of the stromelysin-1 promoter has been implicated as a potential genetic marker for the progression of angiographically determined atherosclerosis in patients with coronary artery disease. Recently, a novel interleukin-6 (IL-6) gene functional G/C polymorphism at Ϫ174 in the promoter has also been reported. In this study, we analyzed the relation of these two polymorphisms with carotid artery atherosclerosis in 109 randomly selected, middle-aged men without exercise-induced ischemia. Atherosclerosis was quantified as intimamedia thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (Pϭ0.015) associated with IMT, and this relation remained (Pϭ0.033) after adjustments for age, cardiorespiratory fitness, body mass index, smoking, LDL cholesterol, and systolic blood pressure and for sonographers. The 5A/6A polymorphism independently explained 7% of the variance in carotid bifurcation IMT. The IL-6 polymorphism was also significantly associated (Pϭ0.036) with increased IMT, with men homozygous for the G allele having IMT that was 11% greater than men homozygous for the C allele. Men who were homozygous for both the 6A and G alleles had an covariate adjusted IMT that was 36% greater than men who were homozygous for neither allele (PϽ0.003). These data suggest that genetic factors that predispose to reduced matrix remodeling (stromelysin 6A allele) and to increased inflammation (IL-6 G allele) combine to increase susceptibility for intima-media thickening in the carotid bifurcation, a predilection site for atherosclerosis. Key Words: stromelysin-1 Ⅲ interleukin-6 Ⅲ DNA polymorphism Ⅲ B-mode ultrasonography Ⅲ carotid atherosclerosis Ⅲ population sample

Innate Immunity SNPs are Associated with Risk for Severe Sepsis after Burn Injury

“…[40][41][42] A guanine to cytosine (G→C) substitution at nucleotide -174 of the IL-6 promoter has been reported to affect gene transcription and has been associated with a number of conditions in which inflammation is considered to play a role. 21,43,44 Allelic associations with severe sepsis were evaluated previously for 159 of the 228 patients described in this report. 10 The present study included patients with ≥15% TBSA burns, compared to patients with ≥20% burns in the previous analysis.…”

The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population

“…Interestingly, IL-6 activity and plasma levels have been associated with several hypertensioninduced disturbances, in particular atherosclerosis. 24 Immunohistochemical studies of the human arterial atherosclerotic wall have demonstrated that IL-6 is expressed in the cellular and extracellular deposits in the connective tissue matrix and that atherosclerotic plaques have high levels of IL-6. 25 Studies in ApoE-knockout mice, that spontaneously develop systemic atherosclerosis, also show elevated levels of IL-6 mRNA in the plaque area compared with normal mice.…”

The role of matrix metalloproteinases and polymorphisms of their genes in the development of coronary heart disease

“…Аналіз одержаних даних [74,75] виявив, що особи із 6A-алелем мали нижчу експресію MMP-3, ніж ті, у яких був 5А-алель [50], більші розміри атероми і навіть частіший рестеноз після ангіопластики. 6А-алель асоційований зі зниженням експресії ММР-3 і прискореним розвитком атеросклерозу через підвищення вмісту колагену в позаклітинному матриксі артерій.…”