Association of the -757T>C polymorphism in the CRP gene with circulating C-reactive protein levels and carotid atherosclerosis.
ABSTRACT C-reactive protein (CRP) is an inflammatory protein that may play a role in the pathogenesis of atherosclerosis. CRP gene single nucleotide polymorphisms (SNPs) have been shown to be associated with CRP concentration; however, their independent effect on atherosclerosis has not been yet established. We aimed to determine whether the 5'-flanking -757T>C CRP gene polymorphism is associated with CRP concentration and carotid atherosclerosis.
We genotyped the -757T>C CRP gene SNP and determined the concentration of serum CRP, the intima-media thickness (IMT) of the common carotid artery and the existence of plaque/s in 612 apparently healthy men and women aged 66+/-10 years.
Carriers of the CRP -757C allele presented with higher IMT and higher CRP concentrations (p=0.002, p=0.042, respectively). After adjustment for vascular risk factors, linear regression analysis showed an independent effect of CRP -757C allele on carotid IMT, beyond serum CRP concentrations. This SNP was also associated with carotid plaque occurrence (O.R. 1.74, 95% CI 1.1-2.77, p=0.002).
The present study provides evidence that a genetic variant of CRP gene is associated with carotid atherosclerosis, independently of traditional vascular risk factors. Further large-scale genomic studies are required, which may identify the genetic vulnerable subjects to develop atherosclerosis.
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ABSTRACT: Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log(2)-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85-0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78-0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32-0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.Translational psychiatry. 01/2013; 3:e228.
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ABSTRACT: It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we investigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups: without either increased CIMT (I) or carotid plaque (P): I(-)P(-); with only increased CIMT: I(+)P(-); with only carotid plaque: I(-)P(+); and with both increased CIMT and carotid plaque: I(+)P(+). The presence and severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs) were assessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I(-)P(-)< I(+)P(-)< I(-)P(+)< I(+)P(+) (P<0.0001). For the patients with DWMLs, the grades of both I(+)P(-) and I(+)P(+) were increased significantly compared to I(-)P(-) (P<0.0025, P<0.05, respectively) without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.Journal of Huazhong University of Science and Technology 02/2013; 33(1):69-74. · 0.58 Impact Factor
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ABSTRACT: The antioxidant and anti-inflammatory effects of hexane (HEXA), chloroform (CHLORO), ethyl acetate (EA) and total alcoholic (T. ALCOH) extracts of M. alysson in hypercholesterolemic-fed rabbits were evaluated. Hypercholesterolemia was induced in male rabbits by high cholesterol diet (HCD) (350 mg/Kg) for 8 weeks. Hypercholesterolemic rabbits were allocated into groups, treated with simvastatin (SIM 5 mg/Kg), different extracts of M. alysson at two doses of 250, 500 mg/Kg. A normal control group and an HCD control one were used for comparison. Lipid profile, as well as oxidized low density lipoprotein-cholesterol (ox-LDL-C), myeloperoxidase activity (MPO) and superoxide anion production (O2.-), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were also evaluated. In addition, histological examination of ascending aorta was performed. We found dyslipedemia associated with significant increases in ox-LDL-C 123.5 ± 9.8 nmol MDA/mg non-HDL, MPO activity 0.08 ± 0.05 U/100 mg tissue and O2.- production 3.5 ± 0. 3 nmol cytochrome C reduced /min/g tissue X 10-4 in hypercholerterolemic rabbits. In addition, there was a significant increase in CRP 6.6 ± 0.49 μmol/L and MCP-1 190.9 ± 6.4 pg/ml and its MRNA expression in HCD. Intima appeared thick with thick plaques surrounding the intima and luminal narrowing. SIM, EA and HEXA extracts of M. alysson had lipid lowering effect, decrease in ox-LDL-C, MPO, O2.-, CRP and MCP-1 mRNA expression with improvement of the pathological picture. M. alysson enhanced the stability of plaque, had lipid lowering, anti-inflammatory and anti-oxidant activities.Saudi Pharmaceutical Journal 01/2013; · 0.95 Impact Factor