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ABSTRACT: Natriuretic peptide precursor A (NPPA) is synthesized, stored, and released by atrial myocytes. Previous studies have shown
that NPPA plays a significant role in the regulation of coronary circulation and in atherosclerosis. Rs5065 NPPA gene polymorphism
leads to the translation of NPPA with two additional arginines and has been suggested to be associated with salt-sensitive
hypertension. The purpose of the present study was to investigate the relationship between the rs5065 NPPA gene polymorphism
and the risk of coronary heart disease (CHD) in Chinese Han population. We genotyped the single nucleotide polymorphism (SNP)
rs5065 NPPA in the human NPPA gene in 1861 sex- and age-matched subjects, comprising of 904 CHD cases and 957 controls of
Chinese Han population. Genotyping of SNP was performed with Taqman SNP allelic discrimination assays by means of an ABI 7900HT.
Our study showed that the frequencies of rs5065 NPPA C allele in the case and the control groups were 0.012 and 0.005, respectively.
There was significant difference in C allele frequency distribution between the two groups (OR = 2.607, 95% CI: 1.197–5.678,
P = 0.012). In the case group, there was significant difference between smokers and nonsmokers with subjects carrying C allele
(P = 0.037), and no significant difference in gender, age, fasting total cholesterol (TC), triglycerides (TG), fasting plasma
glucose (FPG), body mass index (BMI), and blood pressure (BP) between the cases and the controls (P>0.05). Our results suggest that the C allele of rs5065 NPPA gene polymorphism may be associated with the risk of CHD.
Frontiers of Medicine in China 04/2012; 3(4):437-442.
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ABSTRACT: Although (GT) ( n ) repeats in heme oxygenase-1 (HO-1) promoter may modulate gene transcriptional activity, the association between (GT) ( n ) repeats polymorphism and risk of coronary heart disease (CHD) from different levels of oxidative stress (OS) is unknown. We determined the allelic frequencies of (GT) ( n ) repeats in the HO-1 gene promoter and plasma malonaldehyde (MDA) as biomarkers of OS in 2,298 pairs of CHD patients and controls in the Chinese population. Furthermore, we measured MDA in culture mediums and HO-1 expressions levels in cell lysates of endothelial cells carrying various (GT) ( n ) genotypes under different concentrations of H(2)O(2). Compared with L/L genotype (>25 repeats) carriers, the adjusted odd ratios for S/S genotype (≤25 repeats) in subjects with different levels of OS (MDA < 1.83, 1.83-2.91, >2.91 μmol/L) were 1.06 (95%CI, 0.75 to 1.49), 0.79 (95%CI, 0.55 to 1.12), and 0.60 (95%CI, 0.44 to 0.81), respectively (P (interaction) = 0.002). In biological experiments, compared with endothelial cells carrying L/L genotype, cells with S/S genotype did not have a significantly higher HO-1 expression under 0 μmol/L H(2)O(2), but displayed a significantly higher HO-1 expression under 50 μmol/L H(2)O(2) (P (interaction) = 0.003). S/S genotype in HO-1 gene promoter is associated with a lower risk of CHD in subjects with higher levels of OS, because under conditions of high OS, the S/S genotype has higher levels of HO-1, an antioxidant.
Cell Stress and Chaperones 11/2011; 17(3):329-38. · 3.01 Impact Factor
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ABSTRACT: Associations between "lipid-related" candidate genes, blood lipid concentrations and coronary artery disease (CHD) risk are not clear. We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population. The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population. Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95% CI 0.50 to 0.81), after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk (P<0.01) comparing with the major allele G. Individuals with GT genotype had the lowest CHD risk. No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population. SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population. However, it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.
Journal of Huazhong University of Science and Technology 08/2011; 31(4):452-6. · 0.38 Impact Factor
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Li Zhou,
Hu Ding,
Xiaomin Zhang,
Meian He,
Suli Huang,
Yujun Xu,
Ying Shi,
Guanglin Cui, Longxian Cheng,
Qing K Wang,
Frank B Hu,
Daowen Wang,
Tangchun Wu
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ABSTRACT: Recent genome-wide association studies (GWAS) have mapped several novel loci influencing blood lipid levels in Caucasians. We sought to explore whether the genetic variants at newly identified lipid-associated loci were associated with CHD susceptibility in a Chinese Han population.
We conducted a two-stage case-control study in a Chinese Han population. The first-stage, consisting of 1,376 CHD cases and 1,376 sex and age- frequency matched controls, examined 5 novel lipid-associated single-nucleotide polymorphisms (SNPs) identified from GWAS among Caucasians in relation to CHD risk in Chinese. We then validated significant SNPs in the second-stage, consisting of 1,269 cases and 2,745 controls. We also tested associations between SNPs within the five novel loci and blood lipid levels in 4,121 controls. We identified two novel SNPs (rs599839 in CELSR2-PSRC1-SORT1 and rs16996148 in NCAN-CILP2) that were significantly associated with reduced CHD risk in Chinese (odds ratios (95% confidence intervals) in the dominant model 0.76 (0.61-0.90; P = 0.001), 0.67 (0.57-0.77; P = 3.4×10(-8)), respectively). Multiple linear regression analyses using dominant model showed that rs599839 was significantly associated with decreased LDL levels (P = 0.022) and rs16996148 was significantly associated with increased LDL and HDL levels (P = 2.9×10(-4) and 0.001, respectively).
We identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.
PLoS ONE 01/2011; 6(11):e27481. · 4.09 Impact Factor
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ABSTRACT: Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.
Cell Stress and Chaperones 03/2010; 15(5):675-86. · 3.01 Impact Factor
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ABSTRACT: There is ample evidence that Hsp70 takes part in the progress of coronary heart disease (CHD). This implies that genetic variants of Hsp70 genes such as HSPA8 (HSC70) gene might contribute to the development of CHD. The present study aimed to investigate whether certain genetic variants of HSPA8 gene are associated with CHD in Han Chinese people.
A total of 2006 subjects (1003 CHD cases and 1003 age- and sex- matched healthy controls) were recruited. Genetic variants in the HSPA8 gene were identified by sequencing of the gene in 60 unrelated Chinese. Four tag single nucleotide polymorphisms (tagSNPs) (rs2236659, rs2276077, rs10892958, and rs1461496) were selected and genotyped. The function of the significant SNP was evaluated using luciferase reporter assays in two cell lines. By sequencing the promoter and all exons and introns of the HSPA8 gene, 23 genetic variants were identified. One promoter SNP rs2236659 was associated with susceptibility to CHD. Carriers of the "C" allele of rs2236659 had decreased CHD risk with odds ratio (OR) of 0.78 (95% CI: 0.62, 0.98; P = 0.033) after adjustment for conventional risk factors. Haplotype analyses indicated that haplotype GCGC contributed to a lower CHD risk (OR = 0.78, 95% CI: 0.65, 0.93; P = 0.006) compared with the common haplotype AGGT. In a transfection assay, the C allele of rs2236659 showed a 37-40% increase in luciferase expression of the reporter gene luciferase in endothelial and non-endothelial cells compared with the T allele.
These findings suggest that genetic variants in HSPA8 gene (especially promoter SNP rs2236659) contribute to the CHD susceptibility by affecting its expression level.
PLoS ONE 01/2010; 5(3):e9684. · 4.09 Impact Factor
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ABSTRACT: The relation between the expression and activity of MMP-9 in C-reactive protein (CRP)-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B (NF-kappaB) was studied to investigate the possible role of CRP in plaque destabilization. Human THP-1 cells were incubated in the presence of CRP at 0 (control group), 25, 50 and 100 microg/mL (CRP groups) for 24 h. In PDTC (a specific NF-kappaB inhibitor) group, the cells were pre-treated with PDTC at 10 micromol/L and then with 100 microg/mL CRP. The conditioned media (CM) and human THP-1 cells in different groups were harvested. MMP-9 expression in CM and human THP-1 cells was measured by ELISA and Western blotting. MMP-9 activity was assessed by fluorogenic substrates. The expression of NF-kappaB inhibitor alpha (IkappaB-alpha) and NF-kappaB P(65) was detected by Western blotting and ELISA respectively. The results showed that CRP increased the expression and activity of MMP-9 in a dose-dependent manner in the human THP-1 cells. Western blotting revealed that IkappaB-alpha expression was decreased in the cells with the concentrations of CRP and ELISA demonstrated that NF-kappaB P65 expression in the CRP-induced cells was increased. After pre-treatment of the cells with PDTC at 10 micromol/L, the decrease in IkappaB-alpha expression and the increase in NF-kappaB P(65) expression in the CRP-induced cells were inhibited, and the expression and activity of MMP-9 were lowered too. It is concluded that increased expression and activity of MMP-9 in CRP-induced human THP-1 cells may be associated with activation of NF-kappaB. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-kappaB activation.
Journal of Huazhong University of Science and Technology 09/2009; 29(4):399-403. · 0.38 Impact Factor
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ABSTRACT: Licorice has been used to treat many ailments including cardiovascular disorders in China for long time. Recent studies have shown that the cardiac actions of licorice have been attributed to its active component, glycyrretinic acid (GA). However, its mechanism remains poorly understood.
The effects of GA on the cardiac sodium currents (I(Na)), L-type calcium currents (I(Ca,L)) and hyperpolarization-activated inward currents (I(f)) were investigated.
Human isoforms of wild-type and DeltaKPQ-mutant type sodium channels were expressed in Xenopus oocytes, and the resulting currents (peak and late I(Na)) were recorded using a two-microelectrode voltage-clamp technique. A perforated patch clamp technique was employed to record I(Ca,L) and I(f) from isolated rabbit sinoatrial node pacemaker cells.
GA inhibited peak I(Na) (33% at 90 microM) and late I(Na) (72% at 90 microM), but caused no significant effects on I(Ca,L) and I(f).
GA blocked cardiac sodium currents, particularly late I(Na.) Our findings might help to understand the traditional use of licorice in the treatment of cardiovascular disorders, because reduction of sodium currents (particularly late I(Na)) would be expected to provide protection from Na(+)-induced Ca(2+) overload and cell damage.
Journal of ethnopharmacology 07/2009; 125(2):318-23. · 2.32 Impact Factor
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ABSTRACT: HSP70 plays crucial roles in endothelial cell apoptosis, which is involved in the early phase and progress of coronary heart disease (CHD). However, the association between polymorphisms of HSP70 genes and the risk of CHD still remains unclear. Our aim was to determine whether genetic variants in the HSPA1A gene are associated with the risk of CHD.
By resequencing and genotyping, the associations of 2 single nucleotide polymorphisms (SNPs) +190G/C (rs1043618) and -110A/C (rs1008438) in the HSPA1A gene with risk of CHD were determined in a 1,003 pairs case-control study. The SNP function was further analyzed using a luciferase reporter assay in two cell lines. The results indicated that +190CC genotype was associated with significantly higher risk of CHD when compared with +190GG genotype (OR = 1.56, 95% CI: 1.10-2.20, P = 0.012), while association between -110A/C polymorphism and CHD was not statistically significant (P>0.05). However, the -110C/+190C haplotype had a significantly higher risk of CHD when compared with the -110A/+190G haplotype (OR = 1.17, 95% CI: 1.01-1.34, P = 0.031). Luciferase reporter assays showed that the +190C allele resulted in 14% ~ 45% reduction in luciferase expression in endothelial and non-endothelial cells when compared with the +190G allele.
The identified genetic variants in the HSPA1A gene combinatorially contribute towards the susceptibility to CHD likely by affecting the level of synthesis of HSP70. This study may provide useful markers for identification of subjects at risk for CHD.
PLoS ONE 02/2009; 4(3):e4851. · 4.09 Impact Factor
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ABSTRACT: Although heat shock protein 60 (Hsp60) is implicated in the pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is uncertain. This study explored the influence of circulating Hsp60 on CHD in a large case-control study, as well as the impact of acute myocardial infarction on Hsp60 levels in a prospective study.
Plasma Hsp60 and anti-Hsp60 antibody levels were determined by immunoassay. In the case-control study (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher in patients with CHD and were related to CHD (OR comparing extreme quartiles=4.14, P<0.0001). This association remained after adjustment for traditional risk factors (P for trend <0.0001). Individuals having high levels of Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater than the median of 38.42 U/mL) were at a greater risk of CHD than those with low levels (OR 2.30, P<0.0001). Stronger additive effects (OR 14.04, P<0.0001) were apparent at higher Hsp60 and anti-Hsp60 antibody levels (>1000 ng/mL and greater than the median of 38.42 U/mL, respectively). The simultaneous presence of high Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes were cumulatively associated with CHD. Individuals who had any 4 or more of these 5 factors had an OR of 38.61 for CHD (P<0.0001) compared with individuals who had none of these factors. For the prospective study, blood was drawn from 20 patients immediately after admission for acute myocardial infarction and 2, 3, and 7 days thereafter. Hsp60 levels were significantly higher on the day of and the day after arrival than 7 days after an acute myocardial infarction (P=0.011 and P=0.026, respectively).
Elevated Hsp60 levels are associated with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine to increase this risk. In addition, acute myocardial infarction induces Hsp60 release.
Circulation 12/2008; 118(25):2687-93. · 14.74 Impact Factor
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ABSTRACT: We aimed to determine whether the single nucleotide polymorphisms (SNPs) on chromosome 9p21 were associated with coronary heart disease (CHD) in a Chinese Han population.
We determined the genotypes of rs2383206 and rs2383207 on chromosome 9p21 in 1360 CHD patients and 1360 age- and sex-frequency-matched controls from an unrelated Chinese Han population. GG genotypes in rs2383207 occurred more frequently in CHD patients compared to controls, and the odds ratio (OR) was 1.52 (95% CI 1.13 to 2.04), after adjusting for conventional risk factors. In stratified analysis, the risk associated with the GG genotype of the two SNPs was stronger in subjects who were males, less than 60 years old, overweight, and smokers. The SNP rs2383207 had significant interactions with gender and smoking (P=0.018 and 0.037, respectively). The risk allele G of rs2383207 plus family history of CHD had a cumulative association with CHD (P for trend, 1.0x10(-6)); the OR for CHD was 4.59 (95% CI 2.52 to 8.37) for those with all the risk factors as compared with subjects without any of the factors.
The SNP rs2383207 on chromosome 9p21 is significantly associated with CHD in Chinese. This SNP combined with family history has a cumulative association with CHD.
Arteriosclerosis Thrombosis and Vascular Biology 09/2008; 28(11):2085-9. · 6.37 Impact Factor
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ABSTRACT: Several studies have suggested an association between antibody to human heat shock protein 60 (anti-Hsp60) and coronary atherosclerosis, but the results have been inconsistent. The aim of this study was to investigate the association between anti-Hsp60 and coronary heart disease (CHD) and to determine whether anti-Hsp60, hypertension, and diabetes have joint effects on CHD risk.
We measured the concentrations of anti-Hsp60 in 1003 CHD patients and 1003 age- and sex-matched control subjects without CHD events.
Concentrations of anti-Hsp60 were significantly higher in CHD patients than in controls. Increasing concentrations of anti-Hsp60 were significantly associated with higher risk of CHD (P for trend <0.0001) and with increasing severity of CHD as assessed by number of diseased vessels detected with angiography [odds ratio (OR) 3.67, 95% CI 1.56-8.64, P = 0.003] after multivariate adjustment for traditional CHD risk factors. There were strong joint effects of high concentrations of anti-Hsp60 and hypertension (OR 5.17, 95% CI 3.95-6.75, P < 0.0001) and diabetes (OR 6.49, 95% CI 4.52-9.33, P < 0.0001) on CHD risk; simultaneous occurrence of high anti-Hsp60 concentrations, hypertension, and diabetes conferred a dramatically higher risk of CHD (OR 20.99, 95% CI 12.50-35.24, P < 0.0001) in multivariate analyses.
Anti-Hsp60 is independently associated with CHD risk, and a combination of high anti-Hsp60, hypertension, and diabetes is particularly detrimental for CHD risk.
Clinical Chemistry 06/2008; 54(6):1046-52. · 7.91 Impact Factor
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Mei-An He,
Xiaomin Zhang,
Jing Wang, Longxian Cheng,
Li Zhou,
Hesong Zeng,
Feng Wang,
Ying Chen,
Zengguang Xu,
Qingyi Wei,
Frank B Hu,
Tangchun Wu
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ABSTRACT: High levels of circulating heat shock protein 60 (Hsp60) and antibody to human Hsp60 have been associated with greater risk of coronary heart disease (CHD) in several studies, but associations between polymorphisms of the hsp60 gene and CHD risk have not been investigated.
By resequencing DNA from 30 unrelated Han Chinese and using HapMap Phase I Chinese data of hsp60 gene, we selected four tagging single nucleotide polymorphisms (tagSNPs) named rs2340690, rs788016, rs2305560, and rs2565163, and determined their frequencies in 1,003 Chinese CHD patients and 1,003 age- and sex-frequency-matched controls. Furthermore, we used PHASE 2.0 software to reconstruct haplotypes and logistic regression to control for potential confounders in multivariate analyses.
We found 13 SNPs in hsp60 gene (including four novel SNPs) in Han Chinese subjects. Our results showed no significant differences in four selected SNPs in patients with CHD and controls after adjusting for other conventional risk factors and stratifying by age, sex, smoking status, past history of hypertension and DM; however, our results showed that subjects with the GCTC haplotype had about twofold higher risk of CHD than those with the GTTC haplotype (OR = 1.91, 95%CI: 1.26-2.89, P = 0.002).
Our results suggest that the GCTC haplotype in the hsp60 gene is significantly associated with higher CHD risk in a Chinese population.
Cell Stress and Chaperones 04/2008; 13(2):231-8. · 3.01 Impact Factor
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ABSTRACT: In order to investigate the association of G+1688A (Ser563Asn) polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with myocardial infarction (MI) in the Chinese Han population, the G+1688A polymorphism in PECAM-1 gene was detected by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method among 502 subjects, including 218 patients with MI and 284 controls. The results showed that there was significant difference in AA frequencies of genotype G+1688A polymorphism between case and control groups (39% vs 24%, P<0.001). A similar trend was observed on the allele frequencies (A/G: 62% vs 49%, P<0.001). Among the subjects with high serum total cholesterol level or high systolic blood pressure level, the variant AA genotype was associated with high risk of MI (adjusted OR, 2.13; 95% CI, 1.08-4.41 and adjusted OR, 2.53; 95%CI, 1.63-3.63). The single nucleotide polymorphism (SNP) at position +1688 in the exon 8 of PECAM-1 gene was associated with MI and the allele A might be a risk factor for MI in the Chinese Han population.
Journal of Huazhong University of Science and Technology 10/2007; 27(5):520-3. · 0.38 Impact Factor
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ABSTRACT: To explore the role of mechanosensitive potassium channel TREK-1, Western blot analysis was used to investigate the expression changes of TREK-1 in left ventricle in acute mechanically stretched heart. Forty Wistar rats were randomly divided into 8 groups (n=5 in each group), subject to single Langendorff perfusion for 0, 30, 60, 120 min and acute mechanical stretch for 0, 30, 60, 120 min respectively. With Langendorff apparatus, an acute mechanically stretched heart model was established. There was no significant difference in the expression of TREK-1 among single Langendorff perfusion groups (P>0.05). As compared to non-stretched Langendorff-perfused heart, only the expression of TREK-1 in acute mechanically stretched heart (120 min) was greatly increased (P<0.05). This result suggested that some course of mechanical stretch could up-regulate the expression of TREK-1 in left ventricle. TREK-1 might play an important role in mechanoelectric feedback, so it could reduce the occurrence of arrhythmia that was induced by extra mechanical stretch.
Journal of Huazhong University of Science and Technology 08/2007; 27(4):385-7. · 0.38 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is the most common sustained arrhythmia. Because heat shock proteins (Hsp) can protect cells from stress, we compared the levels of Hsp60, Hsp72, Hsc73, and Hsp27 in atrial myocardium from 17 patients with AF (8 paroxysmal and 9 persistent) and 7 controls in sinus rhythm (SR). Hsp60, Hsp72, and Hsc73 levels were not significantly different among the 3 groups. Hsp27 expression was slightly higher in paroxysmal AF than in SR and in persistent AF, and a borderline significant difference (P = 0.064) was seen between the paroxysmal and persistent AF subgroups. Hsp60 levels in the moderate, severe, and profound myolysis groups were significantly lower than the light myolysis group, but no differences were found in other Hsps. In summary, the data indicate that expression of Hsp27 and Hsc73 may be associated with different stages of AF and that Hsp60 also may be associated with the degree of atrial myolysis.
Cell Stress and Chaperones 02/2007; 12(2):142-50. · 3.01 Impact Factor
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ABSTRACT: The expression of stretch-activated potassium channel TREK-1 mRNA and protein of hypertrophic myocardium was measured. Using a model of hypertrophy induced by coarctation of abdominal aorta in male Wistar rats, the expression of TREK-1 mRNA and protein was detected by using semi-quantitative RT PCR and Western blot respectively. At 4th and 8th week after constriction of the abdominal aorta, rats developed significant left ventricular hypertrophy. As compared to sham-operated group, stretch-activated potassium channel TREK-1 mRNA was strongly expressed and protein was up-regulated in operation groups (P < 0.05). It was concluded that the expression of TREK-1 was up-regulated in hypertrophic myocardium induced by chronic pressure overload in Wistar rats.
Journal of Huazhong University of Science and Technology 02/2006; 26(1):31-3. · 0.38 Impact Factor
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ABSTRACT: The association between atrial natriuretic peptide (ANP) polymorphism and coronary heart disease (CHD) was studied in Chinese population. The genotypes of ANP T2238C and ANP C-664G were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods in 158 consecutive CHD patients and 165 controls. It was found that the distribution of A2A2 genotype in CHD group was significantly higher than that in control group (P<0.05). Stepwise Logistic regression analysis revealed that male, smoking, history of hypertension, history of diabetes, family history of hypertension, high level of serum cholesterol, and ANP T2238C polymorphism were the possible risk factors in patients with CHD (P<0.05). However, there was no significant difference between the patients with CHD and the control group in the distribution of ANP C-664G polymorphism (P>0.05). The results suggest that A2A2 T2238C genotype could be one of the risk factors for CHD (P<0.05, OR: 1.80, 95 % CI: 1.03-3.15).
Journal of Huazhong University of Science and Technology 01/2006; 26(5):528-30. · 0.38 Impact Factor
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ABSTRACT: The heat shock proteins (Hsps) are induced by stresses such as allergic factors and inflammatory responses in bronchi epithelial cells and therefore may be detectable in patients with asthma. However, the etiologic link between anti-Hsps and asthma (its severity and related inflammatory responses such as interleukin-4 and immunoglobulin E) has not been established. We determined whether antibodies against Hsp60 and Hsp70 were present in patients with asthma and evaluated their associations with risk and severity of asthma.
We determined the levels of anti-Hsp60 and anti-Hsp70 by immunoblot and their associations with risk and symptom severity of asthma in 95 patients with asthma and 99 matched non-symptomatic controls using multivariate logistic regression analysis.
Compared to the controls, asthma patients were more likely to have detectable anti-Hsp60 (17.2% vs 5.1%) and anti-Hsp70 (33.7% vs 8.1%) (p < or = 0.001). In particular, the presence of anti-Hsp70 was associated with a greater than 2 fold risk for asthma (adjusted OR = 2.21; 95% CI = 1.35 approximately 3.59). Furthermore, both anti-Hsp60 and anti-Hsp70 levels were positively correlated with symptom severity (p < 0.05) as well as interleukin-4 and immunoglobulin E (p < 0.05). Individuals with antibodies against anti-Hsp60 and anti-Hsp70 were more likely to have a family history of asthma (p < 0.001) and higher plasma concentrations of total immunoglobulin E (p = 0.001) and interleukin-4 (p < 0.05) than those without antibodies.
These data suggest that anti-Hsp60 and especially anti-Hsp70 correlate with the attacks and severity of asthma. The underlying molecular mechanisms linking antibodies to heat shock proteins and asthma remain to be investigated.
Respiratory research 02/2005; 6:18. · 3.36 Impact Factor
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Xingfang Jin,
Ruibo Wang,
Chengfeng Xiao, Longxian Cheng,
Feng Wang,
Li Yang,
Taoyi Feng,
Ming Chen,
Sheng Chen,
Xiaoye Fu,
Jie Deng,
Ru Wang,
Fangfang Tang,
Qingyi Wei,
Robert M Tanguay,
Tangchun Wu
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ABSTRACT: Heat shock proteins (Hsps) have been reported to play an important role in both physiological and pathological processes. Hsps also may serve as biomarkers for evaluating disease states and exposure to environmental stresses. Whether Hsp levels in serum and lymphocytes are correlated with age and sex is largely unknown. In this study, we analyzed serum Hsp70 (the most abundant mammalian Hsp) levels by using Western dot blot in 327 healthy male donors aged between 15 and 50 years. We also investigated the association between Hsp70 levels and age in lymphocytes of 80 normal individuals aged between 40 and 77 years because various chronic diseases increase after the age of 40 years. Our data showed that serum Hsp70 levels were positively correlated with age in subjects aged between 15 and 30 years (P < 0.05) but negatively correlated with age in subjects aged between 30 and 50 years (P < 0.05). Serum Hsp70 levels were the highest in individuals aged between 25 and 30 years among all age groups. In the lymphocyte study there also was a significant age-related decrease in Hsp70 levels in lymphocytes of individuals older than 40 years. The Hsp70 levels were negatively correlated with age (r = -3.708, P < 0.0001) but not with sex (r = -10.536, P = 0.452). This suggests that both serum and lymphocyte Hsp70 levels are age-related and that these may be linked to age-related stress. Thus, age is an important factor in using serum and lymphocyte Hsp70 as biomarkers to evaluate the disease states or exposure to environmental stresses (or both).
Cell Stress and Chaperones 04/2004; 9(1):69-75. · 3.01 Impact Factor
