Genomewide linkage analysis for internal carotid artery intimal medial thickness: evidence for linkage to chromosome 12

Carotid intimal medial thickness (IMT) is a heritable quantitative measure of atherosclerosis. A genomewide linkage analysis was conducted to localize a quantitative-trait locus (QTL) influencing carotid IMT. Carotid IMT was measured in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the Framingham Heart Study Offspring cohort. B-mode carotid ultrasonography was used to define mean IMT of the carotid artery segments. Multipoint variance-component linkage analysis was performed. Evidence for significant linkage to internal carotid artery (ICA) IMT (two-point log odds [LOD] score 4.1, multipoint LOD score 3.4) was found 161 cM from the tip of the short arm of chromosome 12; these results were confirmed using the GENEHUNTER package (multipoint LOD score 4.3). No LOD scores >2.0 were observed for common carotid artery (CCA) IMT. Association analysis of a single-nucleotide-polymorphism variant of SCARB1 (minor allele frequency 0.13), a gene in close proximity to the region of peak linkage, revealed a protective association of the missense variant allele in exon 1 of SCARB1, with decreased ICA IMT compared with subjects homozygous for the common allele. Although the exon 1 variant contributed 2% to overall variation in ICA IMT, there was no significant change in the peak LOD score after adjustment in the linkage analyses. These data provide substantial evidence for a QTL on chromosome 12 influencing ICA IMT and for association of a rare variant of SCARB1, or a nearby locus, with ICA IMT. Because this rare SCARB1 variant does not account for our observed linkage, further investigations are warranted to identify additional candidate-gene variants on chromosome 12 predisposing to atherosclerosis phenotypes and clinical vascular disease.     

Analysis of the Interferon Gamma (rs2430561, +874T/A) Functional Gene Variant in Relation to the Presence of Cardiovascular Events in Rheumatoid Arthritis

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA.

Methods

One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA.

Results

Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not.

Conclusion

Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients.     

Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study

Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (-1131T>C, -3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the -1131T >C, -3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.     

冠心病患者颈动脉粥样硬化与血管内皮功能的临床研究价值

目的:探讨颈动脉粥样硬化与血管内皮功能与冠心病患者的相关性。方法:选取114例冠心病患者(54例单支病变和60例多支病变)为观察组和60例健康体检者为对照组,对两组患者动脉粥样硬化及血管内皮功能进行分析。结果:观察组患者TC、TG、HDL及血糖水平均高于对照组,观察组LDL水平显著低于对照组,两组比较差异有统计学意义(P<0.05);观察组患者颈动脉IMT、斑块积分及斑块数明显高于对照组(P<0.05),观察组FMD显著降低(P<0.05),多支病变组病变程度更严重(P<0.05)。结论:颈动脉粥样硬化与血管内皮功能可作为预测冠心病的重要指标,对预防和治疗冠心病具有重要意义。     

Adipokines,inflammation, insulin resistance,and carotid atherosclerosis in patients with rheumatoid arthritis

Introduction

Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Inflammation is thought to be an important factor in accelerated atherosclerosis in RA, whereas insulin resistance is a known risk factor for atherosclerosis in RA. We hypothesised that adipokines could be a link between inflammation, insulin resistance, and atherosclerosis in RA.

Methods

The common carotid artery (CCA) intima-media thickness (IMT), CCA resistive index (RI), and carotid plaques were measured by ultrasonography in 192 patients with RA. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). Serum adiponectin, leptin, resistin, tumor necrosis factor-α, and interleukin (IL)-6 concentrations were determined.

Results

The CCA RI was associated with CCA IMT and the estimated total plaque volume after adjustment for conventional CV risk factors. Among adipokines, resistin and IL-6 were correlated with inflammatory parameters. Leptin and leptin:adiponectin (L:A) ratio were correlated with metabolic risk factors, including HOMA-IR. And L:A ratio was related to the CCA RI after adjustment for conventional and nonconventional CV risk factors, including HOMA-IR, erythrocyte sedimentation rate and C-reactive protein.

Conclusion

L:A ratio was associated with HOMA-IR and carotid RI. L:A ratio might be an independent factor for predicting cardiovascular risk in patients with RA.     

Genetic predisposition to obesity and risk of subclinical atherosclerosis

Obesity has been associated with increased common carotid artery (CCA) intima–media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the association between genetic predisposition to obesity and CCA IMT. The study included 428 young Chinese adults with CCA IMT measured using a high-resolution B-mode tomographic ultrasound system. We created a genetic risk score (GRS) by summing the risk alleles of 6 obesity-associated genetic variants confirmed in our previous analyses. The GRS was significantly associated with greater CCA IMT (p < 0.001) after adjustment for age and gender. Per 2 alleles of the GRS was related to 0.023 mm increment in IMT. The association was attenuated by one half with additional adjustment for obesity status, but remained significant (p = 0.009). In addition, we found that blood pressure significantly modified the association between the GRS and CCA IMT (p for interaction = 0.001). The associations between the GRS and CCA IMT were stronger in participants with systolic blood pressure (SBP) ≥ 120 mm Hg and/or diastolic blood pressure (DBP) ≥ 80 mm Hg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA IMT, p for trend < 0.001) than those with SBP < 120 mm Hg and DBP < 80 mm Hg (per 2 allele increment of the GRS relating to 0.001 smaller CCA IMT, p for trend = 0.930). Our data provides suggestive evidence supporting the potential causal relation between obesity and development of subclinical atherosclerosis. Elevated blood pressure might amplify the adverse effect of obesity on cardiovascular risk.     

Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population

Background and Purpose

The lectin-like oxidised LDL receptor-1 (OLR1) gene encodes a scavenger receptor implicated in the pathogenesis of atherosclerosis. Although functional roles have been suggested for two variants, epidemiological studies on OLR1 have been inconsistent. Methods - We tested the association between the non-synonymous substitution K167N (rs11053646) and intima media thickness of the common carotid artery (CCA-IMT) in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study).

Results

Significantly increased IMT was observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotype. Functional analysis on macrophages suggested a decreased association to Ox-LDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers.

Conclusions

These data suggest that the 167N variant of LOX-1 receptor affects the atherogenic process in the carotid artery prior to evidence of disease through an inflammatory process.     

彩色多普勒超声检查评估老年退行性心脏瓣膜病与颈动脉粥样硬化的相关性研究

目的:应用彩色多普勒超声评估老年退行性心脏瓣膜病(SDHVD)与颈动脉粥样硬化相关性。方法:选择2016年5月-2018年7月中国医科大学航空总医院收治的老年SDHVD患者240例作为观察组,根据心瓣膜钙化程度分级标准将所有患者分为1级组61例、2级组84例以及3级组95例。另取同期于我院住院治疗的非SDHVD患者100例作为对照组。所有患者均接受彩色多普勒超声检查,比较观察组与对照组患者的基础疾病合并情况,对比不同组别患者颈动脉内膜中层厚度(IMT)、颈动脉斑块积分以及颈动脉管腔狭窄程度情况,分析SDHVD与颈动脉粥样硬化相关性。结果:观察组冠心病、糖尿病、高血压以及高脂血症发生率分别为47.08%、50.42%、93.75%、81.67%,均分别高于对照组的24.00%、29.00%、68.00%、52.00%(P0.05)。对照组、1级组、2级组、3级组的IMT以及颈动脉斑块积分比较存在统计学差异,且随着心瓣膜钙化程度分级的逐渐提高,IMT以及颈动脉斑块积分呈逐渐上升趋势(P0.05)。随着心瓣膜钙化程度分级的逐渐升高,颈动脉管腔狭窄程度在50%-70%以及71%-99%中的发生率呈逐渐升高趋势(P0.05)。经Pearson相关性分析显示:SDHVD严重程度与IMT、颈动脉斑块积分以及颈动脉管腔狭窄程度均呈正相关(P0.05)。结论:彩色多普勒超声检查可有效评估SDHVD与颈动脉粥样硬化的严重程度,且SDHVD患者多并发基础疾病,临床应积极预防。     

瑞舒伐他汀治疗颈动脉粥样硬化斑块的临床研究

目的:研究瑞舒伐他汀对颈动脉粥样硬化斑块的治疗效果。方法:将在本院接受治疗的250例颈动脉粥样硬化斑块患者随机分成治疗组125例和对照组125例,治疗组服用瑞舒伐他汀10mg/晚,对照组行其他非瑞舒伐他汀药物治疗,进行为期6个月的观察对比。结果:治疗组治疗后总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)水平显著下降,高密度脂蛋白(HDL)水平显著升高(P<0.05),颈动脉内膜-中层厚度(IMT)、斑块面积变小,与治疗前比较,差异有统计学意义(P<0.05);对照组治疗前后无显著性差异(P>0.05)。结论:瑞舒伐他汀对降低血脂、减缓不稳定型心绞痛早期动脉粥样硬化、稳定斑块和预防脑血管疾病起到非常重要的作用。     

Study of Association of CD40-CD154 Gene Polymorphisms with Disease Susceptibility and Cardiovascular Risk in Spanish Rheumatoid Arthritis Patients

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients.

Methods

One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography.

Results

Nominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p = 0.038). Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p = 0.0047) between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis.

Conclusion

Data from our pilot study indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also, the CD40 rs1535045 gene variant may influence development of subclinical atherosclerosis in RA patients.     

Polymorphisms in the SAA1/2 gene are associated with carotid intima media thickness in healthy Han Chinese subjects: the Cardiovascular Risk Survey

Background

Serum amyloid A protein (SAA) is not only an inflammatory factor, but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein (HDL), which has been linked to atherosclerosis. However, the relationship between genetic polymorphisms of SAA and the intima-media thickness (IMT) of the common carotid artery in healthy subjects remains unclear. We investigated the role of SAA1 and SAA2 gene polymorphisms with IMT in a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study.

Methodology/Principal Findings

Anthropometric and B-mode ultrasound of the carotid IMT were measured in 1914 subjects (849 men; 1065 women) recruited from seven cities in Xinjiang province, (western China). Four SNPs (rs12218, rs2229338, rs1059559, and rs2468844) were genotyped by use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The SNP rs12218 was associated with carotid IMT by analyses of a dominate model (P<0.001) and additive model (P = 0.003), and the difference remained significant after multivariate adjustment (P = 0.008, P<0.001, respectively). This relationship was also observed in rs2468844 after multivariate adjustment by recessive model analysis (P = 0.011) but this was not observed in rs2229338 and rs1059559 before and after multivariate adjustment. These associations were not modified by serum HDL concentration. Furthermore, there were significant interactions between rs2468844 and rs12218 (interaction P<0.001) and rs2229338 (interaction P = 0.001) on carotid IMT.

Conclusion/Significance

Both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects.     

痛风患者血管内皮功能及颈动脉粥样硬化的临床研究

目的:观察痛风患者氧化应激指标与颈动脉内膜中层厚度(IMT)的变化,探讨高尿酸引起内皮功能损伤和颈动脉粥样硬化的机制。方法:选择痛风患者123例,正常健康者116例,检测两组患者血尿酸、细胞间粘附分子1(ICAM-1)、内皮素-1(ET-1)、一氧化氮(NO)、纤溶酶原激活抑制剂-1(PAI-1)、收缩压、舒张压、空腹血糖、HDL-C、LDL-C、TC、TG等糖、脂代谢指标及颈动脉内膜中层厚度(IMT)。分析痛风患者内皮损伤相关因子水平和颈动脉IMT的关系。结果:痛风组血清细胞间粘附分子1(ICAM-1)、内皮素-1(ET-1)、纤溶酶原激活抑制剂-1(PAI-1)水平较对照组增高,颈动脉IMT明显增厚,NO水平较对照组降低,差异均有统计学意义(P0.05)。血尿酸水平、ICAM-1、ET-1、PAI-1与IMT密切相关(P0.01)。结论:痛风患者较对照组存在更明显的代谢紊乱,血管内皮功能损伤,更易发生动脉粥样硬化。     

Atherosclerotic plaques occur in absence of intima-media thickening in both systemic sclerosis and systemic lupus erythematosus: a duplexsonography study of carotid and femoral arteries and follow-up for cardiovascular events

Introduction

The objective of this cross-sectional and retrospective cohort study was (1) to determine the usefulness of intima-media thickness (IMT) in contrast to plaque assessment, (2) to examine the value of additive femoral artery sonography and (3) to identify potential risk factors for atherosclerosis and incident cardiovascular events in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients.

Methods

In this study, 90 SSc and 100 SLE patients were examined by duplexsonography. IMT was measured in common carotid and common femoral arteries, plaques were assessed in common, internal and external carotid and common, proximal superficial and deep femoral arteries. Different definitions of pathological IMT (pIMT) were compared with the presence of plaque. Results were evaluated in relation to traditional and non-traditional risk factors for baseline atherosclerosis (logistic regression) and their predictive value for cardiovascular events during follow-up (cox regression).

Results

Definite atherosclerosis occurred frequently without signs of subclinical atherosclerosis in both diseases: pIMT >0.9 mm was present in only 17/59 (28.9%) SSc and 13/49 (26.5%) SLE patients with already present atherosclerotic plaques. Using age-adjusted pIMT definitions, this rate was even lower (5.1-10.3% in SSc, 14.3-26.5% in SLE). Plaques were located only at the carotid or only at the femoral arteries in 26 (13.7%) and 24 (12.6%) patients, respectively. Age and nicotine pack-years were independently associated with atherosclerotic plaques in SLE and SSc patients, as well as the cumulative prednisolone dose in SSc subgroup, and ssDNA positive SLE patients had a lower risk for atherosclerotic plaque. During follow-up (available for 129/190 (67.9%) patients, 650 person-years), cardiovascular events occurred more often in patients with coronary heart disease (adjusted-hazards ratio (HR) 10.19, 95% confidence interval (CI) 3.04 to 34.17, P <0.001), male patients (adjusted-HR 8.78, 95% CI 2.73 to 28.19, P <0.001) and in patients with coexistent carotid and femoral plaques (adjusted-HR 5.92, 95% CI 1.55 to 22.67, P = 0.009). Patients with solely carotid or femoral plaque were not at higher risk.

Conclusion

Atherosclerotic plaque lesions can be found frequently in absence of intima-media thickening in both SSc and SLE patients. As well as routine sonography of carotid arteries, the sonography of femoral arteries is recommended to identify additional atherosclerotic lesions and to detect patients at a high risk for cardiovascular events.     

Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.     

Association study of MIA3 rs17465637 polymorphism with cardiovascular disease in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. Melanoma inhibitor protein 3 (MIA3) is required for the export of collagen VlI (COL7A1) from the endoplasmic reticulum and it appears to be a tumor suppressor of malignant melanoma. Genome-wide association studies have described an association between MIA3 rs17465637 A/C polymorphisms and coronary artery disease and myocardial infarction. Because of that, we assessed the MIA3 rs17465637 polymorphism in 1505 RA Spanish patients stratified according to the presence/absence of cardiovascular (CV) disease. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using carotid ultrasound to establish carotid intima-media wall thickness and carotid plaques and brachial ultrasonography to determine the presence of endothelial dysfunction by flow-mediated endothelium-dependent and independent vasodilatation. MIA3 rs17465637 allele A showed a trend for association with the presence of carotid plaques (odds ratio 1.56, 95% confidence interval [0.96-2.51]; p=0.07). However, apart from an association of the MIA3 rs17465637 A allele with the risk of CV events in RA patients with dyslipidemia (p=0.018), no other significant associations were found between the presence of MIA3 rs17465637 A allele and the risk of suffering CV events or other surrogate markers of atherosclerosis. In conclusion, our results suggest a potential association of the MIA3 rs17465637 with CV disease in dyslipidemic patients with RA. However, additional studies are required to better establish the role of the MIA3 gene in mechanisms leading to the accelerated atherogenesis observed in RA.     

Polymorphism in the Retinoic Acid Metabolizing Enzyme CYP26B1 and the Development of Crohn’s Disease

Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn’s disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.     

急性脑出血患者颈动脉斑块与血清hs CRP 及HbAlc的相关性研究

目的:探究急性脑出血患者颈动脉斑块与血清超敏C反应蛋白(hs-CRP)及糖化血红蛋白(Hb Alc)的相关性。方法:随机选取我院2013年5月至2015年1月脑科收治的急性脑出血患者84例,根据颈动脉粥样硬化标准将所有患者分为单纯脑出血组(n=25)、轻度粥样硬化组(n=34)和重度粥样硬化组(n=25)三组,另选取同期我院健康体检者50人(对照组)。对比分析四组颈总动脉膜厚度(IMT)空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、hs-CRP与Hb Alc水平,分析急性脑出血患者颈动脉斑块的危险因素。结果:四组的IMT、TC、TG、HDL、LDL、hs-CRP和Hb Alc水平差异均具有统计学意义(P0.05),其中hs-CRP和Hb Alc水平在单纯脑出血组轻度粥样硬化组重度粥样硬化组(P0.05);IMT与hs-CRP和Hb Alc均呈现正相关(r=0.388、0.420,P0.05);IMT、hs-CRP和Hb Alc均为颈动脉粥样硬化的危险因素(OR=3.065、1.978、1.647,P0.05)。结论:急性脑出血患者体内hs-CRP及Hb Alc水平是颈动脉斑块形成的危险因素。     

Polymorphism of stromal cell-derived factor-1 selectively upregulates gene expression and is associated with increased susceptibility to coronary artery disease

Stromal cell-derived factor-1 (SDF-1) plays critical roles in vascular development and hematopoiesis. Here, we investigated the function of SDF-1 rs1801157G/A polymorphism in various immune cells and examined its association with susceptibility to coronary artery disease (CAD). Protein and mRNA levels of SDF-1 were tested in peripheral CD4+ T cell, CD8+ T cells, monocytes, and natural killer (NK) T cells from healthy donors with different genotypes of rs1801157G/A polymorphism. Prevalence of the polymorphism was compared between CAD patients and healthy controls. Data revealed that SDF-1 mRNA and protein were detectable in CD4+ T cells, CD8+ T cells, monocytes and NK T cells. Interestingly, both protein level and mRNA level of SDF-1 were significantly increased in the monocytes with rs1801157AA genotype, whereas the same phenomenon was not observed in the other three cell types. Blockage of CD14 completely inhibited the upregulation of SDF-1 in the monocytes with rs1801157AA genotype. Association analysis showed that frequencies of the rs1801157AA genotype and A allele were significantly higher in CAD cases than in controls (odds ratio [OR] = 2.28, 95% confidence interval [CI], 1.50–3.29, p < 0.0001, and OR = 1.46, 95% CI, 1.21–3.73, p < 0.0001, respectively). Also, prevalence of rs1801157AA genotype was further increased in cases with ST-elevation myocardial infarction (OR = 1.65, 95% CI, 1.04–2.56, p = 0.028). Our data suggest a novel pathway for regulating SDF-1 and a new risk factor for CAD.     

Hcy, hs-CRP与急性脑梗死患者颈动脉粥样硬化关系的研究

目的:探讨急性脑梗死患者血清同型半胱氨酸(Hcy)、超敏C反应蛋白(hs-CRP)与颈动脉粥样硬化的相关性及临床意义。方法:收集确诊为急性脑梗死患者90例,对患者进行颈动脉超声检查,根据颈动脉狭窄程度将患者分成颈动脉内膜正常组、轻度狭窄组、中-重度狭窄组。比较三组患者斑块检出率、Hcy、hs-CRP水平和IMT厚度,同时对Hcy、hs-CRP与IMT进行相关性分析。结果:中-重度狭窄组斑块检出率为86.4%,显著高于轻度狭窄组和颈动脉内膜正常组(P0.05);颈动脉内膜正常组Hcy、hs-CRP水平以及IMT厚度均显著低于颈动脉轻度狭窄组、中-重度狭窄组(P0.05);hs-CRP与IMT呈正相关(r=0.71,P0.05);Hcy与IMT呈正相关(r=0.79,P0.05)。结论:血清Hcy和hs-CRP水平与颈动脉粥样硬化程度密切相关,Hcy、hs-CRP联合检测对急性脑梗死的早期诊断和预后有着重要临床意义。