Association between OLR1 K167N SNP and Intima Media Thickness of the Common Carotid Artery in the General Population

Predazzi, Irene; Norata, Giuseppe Danilo; Vecchione, Lucia; Garlaschelli, K.; Amati, Francesca; Grigore, Liliana; Cutuli, Lucia; Pirillo, Angela; Tramontana, S; Romeo, Francesco; Novelli, Giuseppe; Catapano, Alberico L.

doi:10.1371/journal.pone.0031086

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…Among them, ultrasound detection and quantification of the common carotid artery wall thickness (intima-media thickness, IMT) are considered a surrogate marker of subclinical atherosclerosis [93, 94]. The association between the nonsynonymous substitution K167N (rs11053646) and IMT has been tested in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study) [95]. Significantly increased IMT has been observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotypes [95].…”

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

“…The association between the nonsynonymous substitution K167N (rs11053646) and IMT has been tested in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study) [95]. Significantly increased IMT has been observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotypes [95]. A gender-specific association has been also described between the C (N) allele and prevalence of carotid plaque also in a cohort of Dominican-Hispanic origin [96].…”

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

“…Functional analysis on macrophages suggests a decreased association to OxLDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression [95]. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers [95].…”

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

“…Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers [95]. How these data, obtained with human primary macrophages, relate with those obtained in a transfected fibroblast-like cell line derived from monkey kidney tissue is unclear, and further studies are warranted to clarify this issue [88].…”

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

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LOX-1, OxLDL, and Atherosclerosis

Pirillo

Norata

Catapano

2013

Mediators of Inflammation

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606

511

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Oxidized low-density lipoprotein (OxLDL) contributes to the atherosclerotic plaque formation and progression by several mechanisms, including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation. Vascular wall cells express on their surface several scavenger receptors that mediate the cellular effects of OxLDL. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells, and it is expressed also in macrophages and smooth muscle cells. LOX-1 is almost undetectable under physiological conditions, but it is upregulated following the exposure to several proinflammatory and proatherogenic stimuli and can be detected in animal and human atherosclerotic lesions. The key contribution of LOX-1 to the atherogenic process has been confirmed in animal models; LOX-1 knockout mice exhibit reduced intima thickness and inflammation and increased expression of protective factors; on the contrary, LOX-1 overexpressing mice present an accelerated atherosclerotic lesion formation which is associated with increased inflammation. In humans, LOX-1 gene polymorphisms were associated with increased susceptibility to myocardial infarction. Inhibition of the LOX-1 receptor with chemicals or antisense nucleotides is currently being investigated and represents an emerging approach for controlling OxLDL-LOX-1 mediated proatherogenic effects.

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Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

Section: Genetics Of Lox-1 and Atherosclerosismentioning

confidence: 99%

See 2 more Smart Citations

LOX-1, OxLDL, and Atherosclerosis

Pirillo

Norata

Catapano

2013

Mediators of Inflammation

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606

511

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“…Carotid IMT, as measured by highresolution ultrasound, is a widely used marker of subclinical atherosclerosis. Previous studies have shown associations of genotype and IMT (40), and increased IMT has been associated with increased risk of MI and stroke (4,40,41). In the present study, we chose to use this established measurement of subclinical atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Human Genetic Evidence for Involvement of CD137 in Atherosclerosis

Söderström

Gertow

Folkersen

et al. 2014

Mol Med

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Atherosclerosis is an inflammatory disease and the main cause of cardiovascular disease. Inflammation promotes plaque instability and clinical disease, such as myocardial infarction, stroke and peripheral vascular disease. Subclinical atherosclerosis begins with thickening of the arterial intimal layer, and increased intima-media thickness (IMT) in the carotid artery is a widely used measurement of subclinical atherosclerosis. Activation of CD137 (tumor necrosis factor receptor super family 9) promotes inflammation and disease development in murine atherosclerosis. CD137 is expressed in human atherosclerosis, but its role is largely unknown. This study uses a genetic approach to investigate CD137 in human atherosclerotic disease. In publicly available data on genotype and gene expression from the HapMap project, the minor T allele of rs2453021, a single nucleotide polymorphism in CD137, was significantly associated with CD137 gene expression. In the PROCARDIS and Wellcome Trust Case Control Consortium (WTCCC) cohorts of 13,029 cases and controls, no significant association was detected between the minor T allele of rs2453021 and risk for coronary artery disease or myocardial infarction. However, in the IMPROVE multicenter study of 3,418 individuals, the minor T allele of rs2453021 was associated with increased IMT of the common carotid artery (CCA), as measured by ultrasonography, with presence of plaque in CCA and with increased incidence of adverse noncardiac vascular events. Taken together, this study shows that the minor T allele of rs2453021 is associated with increased IMT in the CCA and increased risk of incident noncardiac vascular events, thus providing the first human genetic evidence for involvement of CD137 in atherosclerosis.

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Abdominal visceral fat measurement using dual‐energy X‐ray: Association with cardiometabolic risk factors

Rothney

Catapano

Jin

et al. 2013

Obesity

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Objective: To examine the association between cardiometabolic risk factors and visceral adipose tissue (VAT) measurements using a dual-energy X-ray absorptiometry (DXA) based approach. Design and Methods: An analysis of cross-sectional relationships between DXA VAT measured using CoreScan (GE Healthcare) and cardiometabolic indicators was conducted on a sample of 939 subjects (541 females and 398 males; average age, 56 years; average BMI, 26 kg/m 2 ) who had previously undergone a total body DXA scan as well as measurements of key cardiometabolic risk factors. Results: Sex-specific, age-adjusted multivariable regression analysis showed that for both men and women, DXA VAT was significantly associated with increased odds of hypertension, impaired fasting glucose, metabolic syndrome, and type 2 diabetes (P < 0.001). After additional model adjustment for BMI and waist circumference, the odds ratio (per SD change in VAT) for type 2 diabetes was 2.07 for women and 2.25 for men. Similarly, the odds ratio for metabolic syndrome for women was 3.46 and for men was 1.75. Conclusions: VAT measured using DXA showed a significant association with cardiometabolic risk factors and disease. These relationships persist after statistical adjustment for age, BMI, and waist circumference. DXA VAT may provide a new accessible option for quantifying VAT-related cardiometabolic risk.

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Association between OLR1 K167N SNP and Intima Media Thickness of the Common Carotid Artery in the General Population

Cited by 21 publications

References 35 publications

LOX-1, OxLDL, and Atherosclerosis

LOX-1, OxLDL, and Atherosclerosis

Human Genetic Evidence for Involvement of CD137 in Atherosclerosis

Abdominal visceral fat measurement using dual‐energy X‐ray: Association with cardiometabolic risk factors

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