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Li H.-R.,Fujian Provincial Hospital | Chen Y.-S.,Fujian Provincial Hospital | Shao H.,Fujian Provincial Hospital | Han L.-L.,Fujian Key Laboratory of Cardiovascular Disease | Zhang X.-E.,Fujian Provincial Hospital
Chinese Journal of Medical Genetics

Objective: To assess the association between polymorphisms of insulin-like growth factor receptor (IGF-1R and IGF-2R) and genetic susceptibility and non-small-cell lung cancer (NSCLC). Methods: A case-control study of 260 patients with NSCLC and 258 cancer-free subjects from Fujian was carried out. Genotypes of polymorphisms of IGF-1R +1013 and IGF-2R + 1619 were determined by DNA sequencing and polymerase chain reaction-restrictive fragment length polymorphism. Results: (1) Significant differences in allele frequency and genotypes distribution of IGF-1R + 1013 (G/A) were found between the two groups (P<0.05). On multivariate analysis after controlling age and gender, compared with GG genotype of the IGF-1R + 1013 (G/A), the risk of lung cancer for individuals with GA genotype was increased by 0.80 times (95%CI: 1.24-2. 59, P = 0.002), those with AA genotype was increased by 2.56 times (95%CI: 1.78-7.26, P = 0.000), and those with the polymorphic A variant (GA or AA) was increased by 0.98 times (95%CI: 1.39-2.83, P = 0.000). No significant differences in genotypic or allelic frequencies of IGF-2R +1619 (G/A) were found between the two groups (P> 0.05). (2) After stratification of the clinical status, the IGF-1R + 1013 A allele increased the risk of lung squamous cell carcinoma (OR=3.20, 95%CI: 1.75-5.84, P = 0.000), lung adenocarcinoma (OR= 1.55, 95%CI: 1.00-2.41, P = 0.049) and other types of lung cancer (OR=1.96, 95% CI: 1.10-3.49, P = 0.023), but no association was found between the two SNPs and other clinical features. (3) IGF-1R + 1013(G/A) and IGF-2R +1619(G/A) polymorphisms showed a synergic effect (P = 0.003). Conclusion: The common IGF-1R gene polymorphism G1013A may influence the risk of lung cancer. The polymorphisms of IGF-1R + 1013 (G/A) and 1GF-2R +1619 (G/A) have synergistic influence on the risk of lung cancer. Source

Luo Z.,Fujian Medical University | Yan C.,General Hospital of Shenyang Military Command | Yu P.,Fujian Medical University | Bao W.,Fujian Medical University | And 8 more authors.
International Journal of Cardiology

Abstract Background Caspase-3 plays an important role in the initiation and maintenance of atrial fibrillation (AF), but little is known about the role of CASP3 variants in the susceptibility to atrial fibrillation (AF). The purpose of this study was to comprehensively investigate the association between common genetic variants of CASP3 gene and AF in Chinese Han population. Methods and results We investigated the association of five variants in CASP3 and the risk of AF in 889 AF patients and 1015 controls. The genotype distribution of the rs4647602 was significantly different between patients with AF and controls (p < 0.001), and the A allele frequency was significantly higher in AF patients than in controls (61.0% vs 53.2%; p < 0.001). Compared with CC genotype carriers, subjects with AA genotype had significantly increased susceptibility to AF (OR = 1.84, p < 0.001). Multivariable logistic regression analysis showed that the rs4647602 polymorphism was significantly associated with risk of AF under dominant, recessive and additive genetic model (OR, 1.44-1.64; all p < 0.001). There was no association between the other four SNPs (rs6948, rs2696056, rs4647602 and rs4647610) and risk of AF. Conclusion The rs4647602 polymorphism is independently associated with the risk of AF in Chinese Han population. © 2015 Elsevier Ireland Ltd. All rights reserved. Source

Luo Z.,Xiamen University | Yan C.,General Hospital of Shenyang Military Command | Zhang W.,Xiamen University | Shen X.,Fujian Key Laboratory of Cardiovascular Disease | And 7 more authors.
Clinical Chemistry and Laboratory Medicine

Background: The small conductance calcium-activated potassium, subfamily N, member 3 (KCNN3) gene rs13376333 and rs1131820 have been shown to be strongly associated with lone atrial fibrillation (AF), while replication association studies between rs13376333 in KCNN3 gene and risk of AF showed conflicting results. The current study tried to validate the impact of SNP rs13376333 and rs1131820 of KCNN3 gene on the risk of AF in the Chinese Han population. Methods: A total of 889 AF patients and 1015 controls were enrolled. Two hundred and seventy-eight cases of AF were lone AF. KCNN3 gene SNP rs13376333 and rs1131820 were genotyped by allele-specific MALDI-TOF mass spectrometry. Results: The genotype distribution and allele frequency of rs13376333 polymorphism were not different between total AF patients and controls. However, the genotype distribution of rs13376333 polymorphism was significantly different between lone AF and control group (p<0.001); and T allele frequency was significantly higher in lone AF group than that in controls (7.6% vs 3.6%, p<0.001). Multivariable logistic regression analysis showed that T allele carriers of rs13376333 was significantly associated with lone AF (OR=2.31, 95% CI 1.41-3.78, p=0.001). No relationship between rs1131820 polymorphism and total AF or lone AF was found in this study. Conclusions: KCNN3 rs13376333 polymorphism was associated with lone AF in the Chinese Han population and the T allele carriers may be an independent predictive factor for lone AF. © by De Gruyter 2014. Source

Pan B.,Peking University | Yu B.,Peking University | Ren H.,Peking University | Willard B.,Cleveland Clinic | And 11 more authors.
Free Radical Biology and Medicine

High-density lipoprotein (HDL) plays a key role in protecting against atherosclerosis. In cardiovascular disease, HDL can be nitrated and chlorinated by myeloperoxidase (MPO). In this study, we discovered that MPO-oxidized HDL is dysfunctional in promoting endothelial repair compared to normal HDL. Proliferation assay, wound healing, and transwell migration experiments showed that MPO-oxidized HDL was associated with a reduced stimulation of endothelial cell (EC) proliferation and migration. In addition, we found that Akt and ERK1/2 phosphorylation in ECs was significantly lower when ECs were incubated with oxidized HDL compared with normal HDL. To further determine whether oxidized HDL diminished EC migration through the PI3K/Akt and MEK/ERK pathways, we performed experiments with inhibitors of both these pathways. The transwell experiments performed in the presence of these inhibitors showed that the migration capacity was reduced and the differences observed between normal HDL and oxidized HDL were diminished. Furthermore, to study the effects of oxidized HDL on endothelial cells in vivo, we performed a carotid artery electric injury model on nude mice injected with either normal or oxidized HDL. Oxidized HDL inhibited reendothelialization compared to normal HDL in vivo. These findings implicate a key role for MPO-oxidized HDL in the pathogenesis of cardiovascular disease. © 2013 Elsevier Inc. Source

Pan B.,Peking University | Ren H.,Peking University | Ma Y.,Peking University | Liu D.,Peking University | And 12 more authors.
International Journal of Cancer

Epidemiological studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. There is a significant inverse association between high-density lipoprotein (HDL) and the risk and mortality of breast cancer. However, HDL could be modified in various ways in diabetes patients, and this may lead to the altered effects on many different types of cells. In our study, we found that glycation and oxidation levels are significantly higher in HDL from type 2 diabetes mellitus patients compared to that from healthy subjects. Diabetic HDL dramatically had a stronger capability to promote cell proliferation, migration and invasion of breast cancer (as examined both on hormone-independent cells and on hormone-dependent cells). In addition, glycated and oxidized HDL, which were produced in vitro, acted in similar way as diabetic HDL. Diabetic HDL, glycated HDL and oxidized HDL also induced higher synthesis and secretion of VEGF-C, MMP-2 and MMP-9 from malondialdehyde (MDA)-MB-231 cells. It was indicated that diabetic, glycated and oxidized HDL promote MDA-MB-231 cell migration and invasion through ERK and p38 MAPK pathways, and Akt pathway plays an important role as well in MDA-MB-231 cell invasion. The Akt, ERK and p38 MAPK pathways are also involved in VEGF-C and MMP-9 secretion induced by diabetic, glycated and oxidized HDL. Our study demonstrated that glycation and oxidation of HDL in diabetic patients could lead to abnormal actions on MDA-MB-231 cell proliferation, migration and invasion, thereby promoting the progression of breast cancer. This will largely draw the attention of HDL-based treatments in diabetic patients especially those with breast cancer. Copyright © 2011 UICC. Source

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