Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS).
To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes).
A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls.
The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P<3.85×10(-3)). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis<5.43×10(-4)). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI.
Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes.
Journal of Thrombosis and Haemostasis 06/2012; 10(8):1508-14. · 5.73 Impact Factor
ABSTRACT: Psoriasis is an immune disorder involving numerous cytokines. Recent studies have shown that interleukin (IL)-21 plays an important role in a variety of inflammatory and autoimmune diseases. It is highly expressed in psoriatic plaques and promotes the proliferation of epidermis in mice. It seems that IL-21 plays an important role in the pathogenesis of psoriasis. However, whether or not it is elevated in the peripheral blood of patients with psoriasis and is associated with disease severity is unclear. Therefore, our study focuses on serum IL-21 levels and their correlation with disease severity.
To detect serum IL-21 levels in patients with psoriasis and investigate the correlation between these and the Psoriasis Area and Severity Index (PASI) scores.
Blood samples were collected from patients with plaque psoriasis and from healthy control subjects. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay in 37 patients with psoriasis and 37 healthy controls. The PASI scores of patients with psoriasis and their correlation with serum IL-21 levels were evaluated.
Serum IL-21 levels were higher in patients with psoriasis than in healthy controls (P < 0·01). Serum IL-21 levels were positively correlated with PASI scores in the patients with psoriasis (r = 0·471, P < 0·01).
Serum IL-21 levels in patients with psoriasis are elevated and positively correlate with PASI scores. These results indicate that IL-21 may play an important role in the pathogenesis of psoriasis.
British Journal of Dermatology 02/2012; 167(1):191-3. · 3.67 Impact Factor
ABSTRACT: To investigate whether brain iron deposition correlates with motor phenotypic expressions of Parkinson's disease.
We subtyped patients with Parkinson's disease according to their main motor symptoms (tremor, rigidity/bradykinesia) into three subgroups: tremor-dominant subgroup, akinetic/rigid-dominant subgroup, or mixed subgroup. The iron levels in bilateral substantia nigra, globus pallidus, putamen, the head of caudate, and red nucleus of 87 patients and 50 control subjects were assayed by measuring phase values using susceptibility-weighted phase imaging in a 3-tesla magnetic resonance system. The serum ceruloplasmin levels of all subjects were determined.
The bilateral average phase values of the substantia nigra and all other brain regions examined did not correlate with the main motor symptoms of Parkinson's disease in the total patient group or when patients were grouped according to serum ceruloplasmin levels. Significant correlations between serum ceruloplasmin levels and nigral bilateral average phase values were observed in the tremor and akinetic/rigid-dominant subgroups. Analysis of patients without prior dopaminergic medication exhibited similar results. Increased nigral iron content correlated with disease severity as assayed by the Unified Parkinson's Disease Rating Scale motor scores in the PD(AR) subgroup.
These findings suggest that nigral iron deposition, correlating with decreased serum ceruloplasmin levels, is a risk factor in Parkinson's disease across multiple motor phenotypic expressions.
European Journal of Neurology 01/2012; 19(7):969-76. · 3.69 Impact Factor
ABSTRACT: A sensitive and specific method was developed and validated for the determination of mitiglinide in plasma using LC-MS/MS. The effect of gemfibrozil on the pharmacokinetics of orally administered mitiglinide in rats was investigated. The validated method in positive electrospray ionization mode using MRM and fully validated according to commonly accepted criteria. The desired sensitivity of mitiglinide was achieved with an LOQ of 0.5 ng/mL and the short run time was suitable for analysis of the large batches of samples. The method was successfully used to analyze rats plasma samples for application in pharmacokinetic studies. Pharmacokinetic parameters of mitiglinide were determined in rats following oral (0.25, 0.5, 1 mg/kg) administration to rats in the presence and absence of gemfibrozil (1 mg/kg). Compared to those animals in an oral control group (given mitiglinide alone), the area under the plasma concentration-time curve (AUC) of mitiglinide were increased significantly by 2.8, 3.5, 4.1-fold (0.25, 0.5, 1 mg/kg) by gemfibrozil, respectively. Consequently, the bioavailability of mitiglinide in the presence of gemfibrozil was significantly enhanced compared to that in oral control group (only mitiglinide). Gemfibrozil significantly enhanced the oral bioavailability of mitiglinide, suggesting that concurrent use of gemfibrozil and mitiglinide should be monitored closely for potential drug interactions.
Arzneimittel-Forschung 01/2012; 62(1):40-5. · 0.72 Impact Factor
ABSTRACT: To describe the clinical characteristics of malignant gestational trophoblastic tumor after medical abortion used by mifepristone combined with misoprostol and its diagnosis and differential diagnosis from incomplete abortion.
Four cases with malignant gestational trophoblast tumor after medical abortion were presented focusing on the clinical manifestation and the methods of diagnosis and differential diagnosis.
Irregular vaginal bleeding and abnormal high level of beta-human chorionic gonadotropin (hCG) in plasma were the common manifestation of the gestational trophoblast tumour and incomplete abortion after medical abortion. However, beta-hCG of the former after curettage was still higher by dynamic monitoring. Malignant gestational trophoblast tumor showed rich blood flow signal and low blood flow resistance index (RI, RI < 0.5) in uterus in color doppler echography, digital subtraction angiography (DSA) with abnormal enlargement of the arteria of uterine, arteriovenous fistula beside the uterine were the main characteristics of malignant gestational trophoblast tumour.
Pay attention to the early stage malignant gestational trophoblast tumour among patients with abnormal vaginal bleeding after medical abortion. beta-hCG and DSA were the most effective methods to diagnose and differentially diagnose choriocarcinoma from the incomplete abortion among the patients with abnormal vaginal bleeding after medical abortion.
Zhonghua fu chan ke za zhi 12/2000; 35(12):733-5.