-
Jingzhou Chen,
Yufang Zhu,
Yuhua Jiang,
Hui Yu,
Kai Sun, Weihua Song,
Liming Luan,
Kejia Lou,
Youxiang Li,
Peng Jiang,
Qi Pang,
Rutai Hui
[show abstract]
[hide abstract]
ABSTRACT: Abnormalities in type III collagen in the arterial walls cause certain familial intracranial aneurysms (IAs); however, it remains unknown whether COL3A1 variants contribute to the risk of sporadic IAs. To study whether COL3A1 variants are associated with sporadic IAs, the association of COL3A1 variants with sporadic IAs was tested in 298 cases and 488 controls, replicated in an independent population of 192 cases and 1,690 controls, and further verified in 633 patients with intra-cerebral hemorrhage, 1,074 hypertensives, and 1,883 controls. We found that allele A of SNP rs1800255 conferred a 1.71-fold increased risk for IAs (adjusted odds ratio: OR = 1.71, 95% confidence interval: CI 1.19-2.45, P = 0.004) and results in an amino acid change of Ala698Thr, which led to a lower thermal stability of the peptide. These results were confirmed in the independent study. The associations were independent of the presence of hemorrhagic stroke and hypertension. These results support the view that the functional variant of COL3A1 is genetic risk factors for IAs in the Chinese population.
Human Genetics 01/2012; 131(7):1137-43. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine (C-C motif) receptor 2 (CCR2) are implicated in promoting atherosclerosis. Many studies have searched the association between variants of the MCP-1 gene or CCR2 gene and risk of coronary artery disease (CAD), but the results are inconsistent.
We conducted a meta-analysis of 20 publications including 24 studies on 2 genetic variants [A-2518G in the MCP-1 and V64I in the CCR2] published before January 2011, including a total of 9844 patients with CAD and 11,821 controls. Publication bias and heterogeneity among studies were explored.
In a combined analysis, the pooled OR for CAD of the -2518G allele was 1.42 (95%CI: 1.06-1.92) compared to wild-type A allele under a recessive model in Caucasian group, but there is an indication of publication bias and heterogeneity among the 9 studies. When the analyses were restricted to 2 large studies (n≥500 cases), the pooled OR was 1.08 (95%CI: 0.85-1.37). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the CCR2 V64I variant showed no significant association with CAD, the pooled OR of 64I was 1.27 (95%CI: 0.81-1.99) in recessive model and 1.06 (95%CI: 0.95-1.19) in dominant model, respectively.
The results indicate that MCP-1-2518G allele had probably increased risk of CAD in Caucasian but this is likely to be due to publication bias and insufficient sample size. The CCR2 V64I has not been found any association with CAD.
Atherosclerosis 08/2011; 219(1):224-30. · 3.79 Impact Factor
-
Jing Xu,
Wenlong Li,
Xunna Bao,
Hu Ding,
Jingzhou Chen,
Weili Zhang,
Kai Sun,
Jizheng Wang,
Xiaojian Wang,
Hu Wang,
Hui Yu, Weihua Song,
Weiwei Ma,
Lin Zhang,
Changxin Wang,
Daowen Wang,
Rutai Hui
[show abstract]
[hide abstract]
ABSTRACT: uPA (urokinase-plasminogen activator) and its receptor (uPAR) have been implicated in a broad spectrum of pathophysiological processes, including fibrinolysis, proteolysis, inflammation, atherogenesis and plaque destabilization, all of which are involved in the pathogenesis of MI (myocardial infarction). We hypothesized that putative functional genetic variation in the two genes encoding uPA and uPAR (PLAU and PLAUR respectively) might influence the susceptibility to MI. We genotyped rs4065 [3'-UTR (untranslated region) *141C>T) and rs2227564 (Pro141Leu) in the PLAU gene as well as rs344781 (-516T>C) in the PLAUR gene in 633 MI patients and 1237 gender- and age-matched control subjects. Our results showed that the T allele of rs4065 was significantly associated with an increased risk of MI, with an adjusted OR (odds ratio) of 1.38 [95% CI (confidence interval), 1.07-1.78; P=0.012) under the dominant model, 1.4 (95% CI, 1.12-1.75; P=0.003) under the additive model and 2.5 (95% CI, 1.15-5.41; P=0.02) under the recessive model. The findings were then replicated in another independent case-control study including 545 MI patients and 597 control subjects. In conclusion, our results suggest that rs4065 might be a previously unknown genetic risk factor for MI in the Chinese Han population.
Clinical Science 10/2010; 119(8):353-9. · 4.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiopoietin-2 has been reported to regulate the inflammation process, which is associated with recurrence of stroke. The purpose of this study was to test the hypothesis that plasma levels of angiopoietin-2 and variants of angiopoietin-2 will confer risk of stroke recurrence. The association of plasma angiopoietin-2 (determined by using ELISA) and the variants in angiopoietin-2 promoter with stroke recurrence was tested in 1735 patients with stroke of three subtypes, lacunar infarct (n=475), atherothrombotic (n=794) and hemorrhage (n=466), for a period of following-up 4.5 years (mean), the association was evaluated by using Kaplan-Meier analysis and the Cox regression models. We found that angiopoietin-2 levels were associated with risk of stroke recurrence in lacunar infarct patients. Taking the lowest quartile as reference, the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for stroke recurrence was 1.48 (0.74-2.95) for the second quartile, 2.56 (1.35-4.86) for the third and 2.15 (1.11-4.17) for the fourth. Allele T of rs3739391 in angiopoietin-2 promoter was associated with elevated angiopoietin-2 levels and increased risk of stroke recurrence in patients with lacunar infarct with HR 1.67 (1.06-2.63) relative to the allele C, but neither in those with atherothrombotic nor in those with hemorrhagic stroke. Our results indicate that both angiopoietin-2 and allele T of rs3739391 might be the risk marker for stroke recurrence in the patients with lacunar infarction. These findings may help to improve future prevention or therapy strategies for stroke. Even some conventional risk factors have been identified responsible for stroke recurrence, but these factors could not fully explain all the recurrent stroke events. Our study opens a new page for the first time that angiopoietin/tie2 pathway has a potential role in lacunar stroke recurrence. Since several strategies are available for blocking or neutralizing plasma angiopoietin-2, especially eicosapentaenoic acid rich in sea food. Our finding obviously has its clinical implication if it was proved by large, prospective clinical studies.
Biochemical and Biophysical Research Communications 07/2010; 398(2):212-6. · 2.48 Impact Factor
-
Jingzhou Chen,
Tao Yang,
Hui Yu,
Kai Sun,
Yi Shi, Weihua Song,
Yongyi Bai,
Xiaojian Wang,
Kejia Lou,
Yan Song,
Yinhui Zhang,
Rutai Hui
[show abstract]
[hide abstract]
ABSTRACT: Angiopoietin-1 is a vascular strengthening factor during vascular development and a protective factor for pathological vascular inflammation and leakage. Brain vascular leaking and inflammation are two important pathological processes of stroke; therefore, we hypothesized that variants of the microRNA-binding site in angiopoietin-1 would affect its expression and confer a risk of stroke. To test our hypothesis, a predicted microRNA-binding site was found in the 3'-UTR of angiopoietin-1 using bioinformatics; variant rs2507800 was identified to be located in the miR-211-binding site of angiopoietin-1. Secondly, the effects of the identified variant on angiopoietin-1 translation were assessed using a luciferase reporter assay and ELISA. We found that the A allele of rs2507800 suppressed angiopoietin-1 translation by facilitating miR-211 binding, but not the T allele. Subjects carrying the TT genotype had higher plasma angiopoietin-1 levels than those with the A allele. Finally, the association of the variant with stroke was tested in 438 stroke patients and 890 controls, and replicated in an independent population of 1791 stroke patients and 1843 controls. The TT genotype resulted in a significant reduction in overall stroke risk {OR, 0.51 [95% confidence interval (CI), 0.36-0.74], P = 0.0003}, ischemic stroke [OR, 0.56 (95% CI, 0.36-0.85), P = 0.007] and hemorrhagic stroke [OR, 0.46 (95% CI, 0.26-0.80), P = 0.007]. These results were confirmed in an independent study. Our results provide evidence that the TT genotype (rs2507800) in the 3'-UTR of angiopoietin-1 might reduce the risk of stroke by interfering with miR-211 binding.
Human Molecular Genetics 04/2010; 19(12):2524-33. · 7.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: C-reactive protein (CRP) has been shown to contribute to the risk of cardiovascular disease. Several single nucleotide polymorphisms (SNPs) at the CRP locus have been found to be associated with CRP concentrations. We hypothesized that genetic variants associated with high CRP may confer a greater risk of stroke and recurrence. The hypothesis was tested in a case-control study and during follow-up of the case population.
Two genetic variants associated with serum CRP in the CRP gene were genotyped in a Chinese case-control study comprised of 1572 stroke patients and 1485 controls. The case population was followed for a median of 4.5 years (range, 0.1-6.0 years).
During a median 4.5-year follow-up for 1526 stroke patients, 299 recurrent strokes were identified. No association was found between the SNPs or haplotypes of the CRP gene and stroke and its recurrence.
Although these variants and corresponding haplotypes in the CRP gene are associated with serum CRP concentrations, our study does not support that variants and corresponding haplotypes studied here have a major influence on risk of stroke and stroke recurrence. Therefore, we speculate that CRP is not a causal factor for stroke.
Clinical Chemistry and Laboratory Medicine 02/2010; 48(4):551-4. · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiopoietin-2 is an important mediator of angiogenesis, and we hypothesized that genetic variants of ANGPT2 (the gene encoding angiopoietin-2) would result in abnormal angiogenesis and contribute to stroke susceptibility. To test our hypothesis, we investigated the association of variants in the promoter of ANGPT2 with stroke in a multi-centre case-control study. We found that the C allele of rs3739390 conferred a 1.42-fold risk of lacunar infarction {adjusted OR (odds ratio), 1.42 [95% CI (confidence interval), 1.08-1.87]; P=0.012} and a 2.10-fold higher transcriptional activity than did the corresponding G allele rs3739390G. The haplotype G-G-T conferred a 1.54-fold risk of atherothrombotic stroke and a 1.64-fold risk for haemorrhagic stroke, whereas the haplotype G-C-C conferred approx. a 2.0-fold risk of each subtype of stroke. In conclusion, our results indicate that haplotypes in the promoter of ANGPT2 confer a high risk of stroke in a Chinese population.
Clinical Science 05/2009; 117(11):387-95. · 4.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Perilipin is encoded by the gene PLIN and mediates lipid metabolism. Its upregulation has been linked to the formation of foam cells, rupture of atherosclerotic plaques, and perhaps acute coronary syndrome. We hypothesized that genetic variations in PLIN might contribute to the susceptibility to stroke. The hypothesis was tested in 2 case-control studies.
Six PLIN tag single nucleotide polymorphisms (rs7176403, rs8179078, rs6496589, rs8179043, rs894160, rs1052700) were genotyped in 1571 patients with stroke (690 cerebral thrombosis, 429 lacunar infarction, 452 intracerebral hemorrhage) and 1638 control subjects. A SHEsis software platform was used to analyze pairwise linkage disequilibrium and haplotype association in the case-control study. The study was replicated in another independent case-control study including 120 patients with stroke and 240 control subjects.
No association of the PLIN variants with stroke (P>0.05) or with stroke subtypes (P>0.05) was found in the first study. The findings were confirmed in the second population (P>0.05).
The data represent an important negative finding that the common variants of PLIN do not have a major effect on susceptibility to stroke in a Chinese population.
Stroke 02/2008; 39(2):470-2. · 5.73 Impact Factor
