Association of adiponectin and its receptor gene polymorphisms with the risk of coronary heart disease in northern Guangxi.

OBJECTIVE: To investigate the association of circulating adiponectin (APN) level and single nucleotide polymorphisms (rs1501299 and rs266729) of the APN gene in the coronary heart disease (CHD) population of Northern Guangxi Province. METHODS: Two hundred and sixty-three CHD patients and 235 healthy controls from our hospital from August 2018 to October 2020 were included in this study. ELISA was used to determine the serum APN concentration. PCR-RFLP and direct DNA sequencing were used to analyze the genotypes of APN gene rs1501299 G/T and rs266729 C/G single-nucleotide loci, their distribution differences between the two groups were compared and their correlation with APN concentration was analyzed. RESULTS: The serum APN concentration in the CHD group was significantly lower than the control group (14.40(1.42-52.26) µg/mL vs. 29.40 (3.18-90.31) µg/mL, P < 0.001). There were statistically significant differences in the rs266729 genotype of APN single nucleotide locus between the two groups (P < 0.001). The dominant model and recessive model of rs266729 genotype showed that mutant homozygous GG genotype carriers significantly increased the risk of CHD in comparison with C allele carriers (CG + CC) (OR = 2.156, 95 %CI: 1.004-4.631, P = 0.049), and this effect was still significant after adjusting gender and age (OR = 2.695, 95 %CI 1.110-6.540, P = 0.028). In both the dominant and recessive models for rs1501299, ORs before and after adjustment for age and sex revealed no significant association with CHD, with ORs of 0.765 (95 % CI: 0.537-1.091, P = 0.139) and 0.718 (95 % CI: 0.466-1.106, P = 0.133) in the Dominant model, and ORs of 0.960 (95 % CI: 0.442-2.087, P = 0.918) and 0.613 (95 % CI: 0.239-1.570, P = 0.308) in the Recessive model, respectively. No statistically significant differences in APN concentrations across genotypes in both groups (P > 0.05), with chi-square values of 1.633 (control group) and 0.823 (CHD group) for rs1501299, and 1.354 (control group) and 0.618 (CHD group) for rs266729. CONCLUSIONS: APN gene of rs266729 C/G single-nucleotide loci gene mutation can significantly increase the risk of CHD. There was no significant correlation between rs1501299 G/T single-nucleotide loci and CHD in Northern Guangxi populations.

Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. Current evidence shows that the CD40-CD40L system plays a crucial role in the development, progression and outcome of SLE. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to SLE and its impact on CD40 expression in Chinese. We analyzed four single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs13040307C/T, rs752118C/T, and rs3765459G/A in 205 patients with SLE and 220 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble CD40 (sCD40) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832 C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 T variant allele were associated with increased CD40 levels compared with the homozygous wild-type genotype in patients with SLE. The rs1883832 C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. These data suggest that CD40 gene may play an essential role in the development of SLE.

The association of CD40 polymorphisms with CD40 serum levels and risk of systemic lupus erythematosus.

BACKGROUND: Current evidence shows that the CD40-CD40 ligand (CD40-CD40L) system plays a crucial role in the development, progression and outcome of systemic lupus erythematosus (SLE). The aim of this study was to investigate whether a CD40 gene single nucleotide polymorphism (SNP) is associated with SLE and CD40 expression in the Chinese population. We included controls (n = 220) and patients with either SLE (n =205) in the study. METHODS: The gene polymorphism was measured using Snapshot SNP genotyping assays and confirmed by sequencing. We analyzed three single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs1569723A/C and rs4810485G/T in 205 patients with SLE and 220 age-and sex-matched controls. Soluble CD40 (sCD40) levels were measured by ELISA. RESULTS: There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 C/T variant allele were associated with increased CD40 levels compared to the homozygous wild-type genotype in patients with SLE. The rs1883832C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. CONCLUSIONS: Our results suggest that CD40 gene may play a role in the development of SLE in the Chinese population.

Meta-analysis of the association of the rs2234693 and rs9340799 polymorphisms of estrogen receptor alpha gene with coronary heart disease risk in Chinese Han population.

OBJECTIVE: The association between a common variant of the ESR1 gene rs2234693 and rs9340799 polymorphisms with coronary heart disease (CHD) have been reported, but the available data on this relationship are inconsistent. A meta-analysis was performed to quantitative analysis the association of ESR1 gene polymorphisms and CHD risk using previous case-control studies in Chinese Han population. METHODS: Several electronic databases were searched for relevant articles up to August 2012. After data collection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Different effect models were used according to the difference in heterogeneity. Sensitivity analysis was assessed by omitting one study at a time. Publication bias was examined using Begg's funnel plot and Egger's linear regression test. RESULTS: Ten studies covering 3400 subjects on rs2234693 and rs9340799 polymorphisms in the ESR1 gene with CHD risk was included in this meta-analysis. For rs2234693 polymorphism, ten studies were combined to the meta-analysis. A significantly increased CHD risk was found in a dominant model (OR=1.35, 955 CI=1.01-1.81, P=0.05), recessive model (OR=1.40, 95% CI=1.15-1.69, P=0.0007), and additive model (OR=1.67, 95% CI=1.19-2.34, P=0.003). Subgroup for male but not for female showed that the CC genotype could increase the risk of CHD compared with TT and TC genotype in Chinese Han population. Concerning rs9340799 polymorphism, eight studies were combined to the meta-analysis. And no evidence of significant association with CHD risk was found in all genetic models. CONCLUSION: Our meta-analysis of 10 studies involving Chinese Han population suggests that the CC genotype of the ESR1 rs2234693 polymorphism is significantly associated with an increased risk of CHD in males only. There was no evidence however, of a significant association between the ESR1 rs9340799 polymorphism and CHD risk.

Tumor-suppressive effects of 1, 25-dihydroxyvitamin D3 in gastric cancer cells.

BACKGROUNDS/AIMS: It has been previously demonstrated that vitamin D acts as a prognostic indicator of gastric cancer and may be correlated with the incidence risk of gastric cancer. However, the effect of 1,25-dihydroxyvitamin D3 on the apoptosis of human gastric cancer cells is unclear. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 induced the cellular apoptosis of BGC-823 gastric cancer cells and to determine the potential mechanism of action. METHODOLOGY: We demonstrate that 1,25-dihydroxyvitamin D3 induced the apoptosis of gastric cancer cells via the processing of PARP and cleavage of caspase 3. Additionally, an increase in BAX expression and a decrease in ERK1/2 and AKT phosphorylation were associated with 1,25-dihydroxyvitamin D3-induced apoptosis. The mRNA expression levels of VDR, CYP24A1, and p21 were increased significantly following 1,25-dihydroxyvitamin D3 treatment. CONCLUSIONS: These findings suggest that 1,25-dihydroxyvitamin D3 exerts tumor-suppressive effects on BGC-823 human gastric cancer cells.

The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.

[Analysis of Gene Deficiency Types of Thalassemia in Lingui District of Guilin City].

OBJECTIVE: To analyze the gene defect types and distribution characteristics of α- and ß-thalassemia in Lingui District of Guilin City, Guangxi, so as to provide scientific basis for genetic consultation and prevention measures. METHODS: A total of 6 496 suspected cases for screening the thalassemia during physical examination, premarital examination, pregnancy examination and hospitalization in the Second Affiliated Hospital of Guilin Medical University from May 2016 to October 2019 were analyzed. Gap-PCR, PCR-RDB and DNA sequencing techniques were used to detect the types and constituent ratios of gene defects in α- and ß-thalassemia positive cases. RESULTS: Among 6 496 suspected patients, 1 363 were thalassemia carriers, the total positive rate was 20.98%. There were 677 cases of single-gene deletion and 26 cases of double-gene detetion on the deletional α-thalassemia, 115 cases of non-deletion α-thalassemia mutation and 4 cases of deletion plus mutation. The positive rate of α-thalassemia was 12.66%. There were 11 gene abnormalities for α-thalassemia, of which --SEA/αα (50.36%) was the most common, followed by -α3.7/αα (23.84%); the main α-gene mutation was ααCS (6.93%). There were 514 ß-thalassemia gene carriers, with a positive rate of 7.93%. In 12 types of ß-gene mutations, CD41-42 (-TTCT) (55.64%) was the most common, followed by CD17 (A→T) (20.23%). There were 25 cases of double heterozygous α and ß thalassemia (0.39%), of which -α3.7/ßCD17 (24%) and --SEA/ß41-42 (16%) were numerically dominant. Two of rare thalassemia genotypes were identified by sequencing, which were heterozygous mutations of Chinese Hong Kong type α thalassemia (HKαα/αα or HKαα/-α3.7) and ß gene mutations IVS-I (-2) or codon30 (A→G) ß0, respectively. CONCLUSION: Lingui district of Guilin city is a high incidence area of thalassemia. The mutation rate of α-thalassemia --SEA/αα type deletion is relatively high, followed by that of the right deletion type (-α3.7/αα). CD41-42 (-TTCT) has the highest mutation rate in ß-thalassemia, followed by CD17(A→T). The results of this study provide reference data for the regional screening, diagnosis and treatment of thalassemia and eugenics.

Bortezomib inhibits cell proliferation in prostate cancer.

Despite the improvement in chemotherapeutic agents, the outcome of patients with prostate cancer remains poor. It is therefore imperative that new anticancer drugs are explored. The aim of the present study was to investigate the inhibitory effect of bortezomib on DU145 prostate cancer cells. The DU145 cell proliferation rate was detected via MTT assay prior to and following exposure to various concentrations of bortezomib, and the level of cell apoptosis and the cell cycle distribution were tested using flow cytometry. In addition, western blotting was used to measure the expression of Bcl-2-interacting killer (Bik) and active-caspase-3. The results showed that bortezomib inhibited the proliferation of DU145 cells in a time- and dose-dependent manner. Following treatment with 1.6 µmol/l bortezomib, the DU145 cells showed marked nuclear condensation, chromatin condensation and fragmentation. Analysis of the cell cycle revealed a significantly increased percentage of cells in the G0/G1 phase and a decreased percentage in the S and G2/M phases. The rate of DU145 cell apoptosis was significantly higher in the bortezomib group than that in the control group, and this was accompanied by an enhanced expression of Bik and active-caspase-3. It can be concluded that bortezomib inhibits the proliferation of DU145 cells by inducing apoptosis. The underlying mechanism may involve the upregulation of Bik and active-caspase-3 expression.

Synergistic Effect of a Physiological Ratio of Estradiol and Testosterone in the Treatment of Early-stage Atherosclerosis.

BACKGROUND AND AIMS: Clinical trials and epidemiological data suggest that estrogen replacement therapy (ERT) fails to reduce cardiovascular events in postmenopausal women with coronary heart disease (CHD). The high concentration of estrogen supplementation may increase the risk of thrombosis and result in testosterone deficiency, which is considered the main reason for failure. Thus, we hypothesized that a physiologic dosage of estradiol combined with testosterone may become a new therapeutic strategy in postmenopausal women with CHD. METHODS AND RESULTS: We used human umbilical vein endothelial cells (HUVECs) and female C57BL/6 mice as the experimental subjects. With the HUVECs, we found an appropriate E2/T ratio of 5:1 (5×10(-8) mol/L estradiol and 10(-8) mol/L testosterone), which has a significant anti-apoptotic effect on HUVECs by inducing a C-reactive protein. In the in vivo study, we verified the beneficial effects of the defined appropriate E2/T ratio in mice with early stage atherosclerosis. We found that replacement therapy with the defined appropriate E2/T ratio had beneficial effects of reducing the lipid lesions, reducing the formation of foam cells, reducing endothelial injury, modulating the coagulation system function and inhibiting inflammation and was significantly more effective than either estradiol or testosterone supplementation alone. CONCLUSION: The present study demonstrated that estradiol and testosterone have a synergistic effect on early stage atherosclerosis, and replacement therapy with the defined appropriate E2/T ratio can significantly suppress the development of atherosclerosis through reducing the lipid lesions, reducing the formation of foam cells, reducing endothelial injury, modulating the coagulation system function and inhibiting inflammation.

[Relationship between osteopontin gene genetic polymorphisms and susceptibility of nasopharyngeal carcinoma in Guangxi Zhuang people].

OBJECTIVE: To evaluate the relationship between osteopontin gene genetic polymorphisms and susceptibility of nasopharyngeal carcinoma in Guangxi Zhuang people. METHODS: With a hospital based case-control study, osteopontin gene polymorphisms were compared between patients with nasopharyngeal carcinoma and healthy outpatients as a controls in Zhuang population in Guangxi. The single nucleotide polymorphisms at rs1126772 and rs9138 sites of the osteopontin gene were determined by polymerase chain reaction-single base extension technique (PCR-SBE) and DNA sequencing technology. The comparison between genotype and allele frequency distribution differences in case and control group was accomplished by a χ(2) test. The frequencies of haplotypes in osteopontin gene in different groups were analyzed. RESULTS: There were no differences between the patients and controls in the genotype or allele frequencies of osteopontin gene rs1126772 site ( GA/GG: OR = 0.94, 95%CI 0.37-2.37, χ(2) = 0.182, P = 0.891; AA/GG:OR = 0.86, 95%CI 0.35-2.12, χ(2) = 0.834, P = 0.773) or rs9138 site ( CA/CC: OR = 1.42, 95%CI 0.88-2.29, χ(2) = 2.023, P = 0.155; AA/CC:OR = 1.77, 95%CI 0.78-4.01, χ(2) = 1.901, P = 0.168). The frequency of GA haplotype in the patients was significantly higher than that in the controls (P = 0.003), and the GA haplotype was associated with a significantly increased risk of nasopharyngeal carcinoma (OR = 4.84, 95%CI 1.59-14.71). CONCLUSION: The haplotype GA of osteopontin gene rs1126772 and rs9138 sites increases the risk of nasopharyngeal carcinoma in Guangxi Zhuang people.

Association of the single-nucleotide polymorphism and haplotype of the complement receptor 1 gene with malaria.

PURPOSE: Although the polymorphisms of erythrocyte complement receptor type 1 (CR1) in patients with malaria have been extensively studied, a question of whether the polymorphisms of CR1 are associated with severe malaria remains controversial. Furthermore, no study has examined the association of CR1 polymorphisms with malaria in Chinese population. Therefore, we investigated the relationship of CR1 gene polymorphism and malaria in Chinese population. MATERIALS AND METHODS: We analyzed polymorphisms of CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T in 509 patients with malaria and 503 controls, using the Taqman genotyping assay and PCR-direct sequencing. RESULTS: There were no significant differences in the genotype, allele and haplotype frequencies of CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms between patients with malaria and controls. Furthermore, there was no association of polymorphisms in the CR1 gene with the severity of malaria in Chinese population. CONCLUSION: These findings suggest that CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms may not be involved in susceptibility to malaria in Chinese population.

1,25-Dihydroxyvitamin D3 and cisplatin synergistically induce apoptosis and cell cycle arrest in gastric cancer cells.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] plays an anticancer role in multiple types of cancer and potentiates the cytotoxic effects of several common chemotherapeutic agents. The hypercalcemia caused by 1,25(OH)2D3 alone or resistance to cisplatin weaken the anticancer effects of vitamin D. Thus, in this study, we aimed to investigate the synergistic effects of 1,25(OH)2D3 and cisplatin on the apoptosis and cell cycle progression of gastric cancer cells. BGC-823 human gastric cancer cells were treated with 1,25(OH)2D3 or cisplatin alone, or a combination of both agents. Cell apoptosis was assessed by TUNEL assay and flow cytometry. The expression of the apoptosis-related proteins, poly(ADP-ribose) polymerase (PARP), Bax, Bcl-2, caspase-3 and caspase-8, was examined using immunoblot analysis. ERK and AKT phosphorylation were examined by immunoblot analysis. The cell cycle distribution was determined by propidium iodide staining and flow cytometric analysis. p21 and p27 protein expression was also examined using immunoblot analysis. Our results revealed that co-treatment with 1,25(OH)2D3 enhanced cisplatin-induced apoptosis and upregulated the expression of Bax, and promoted the cleavage of PARP and caspase-3. The phosphorylation levels of ERK and AKT were reduced following combined treatment with 1,25(OH)2D3 and cisplatin. The percentage of cells in the G0/G1 phase was greater in the cells treated with the combined treatment than in those treated with either 1,25(OH)2D3 or cisplatin alone. p21 and p27 expression was upregulated following co-treatment with both agents. The results of this study suggest that 1,25(OH)2D3 potentiates cisplatin-mediated cell growth inhibition and cell apoptosis, which involves the upregulation of Bax, a decrease in ERK and AKT phosphorylation levels, and increased p21 and p27 levels.

Single nucleotide polymorphisms of toll-like receptor 7 and toll-like receptor 9 in hepatitis C virus infection patients from central China.

PURPOSE: To analyze the correlation of polymorphisms of toll-like receptor 7 (TLR7) (rs179009) and toll-like receptor 9 (TLR9) (rs187084) in hepatitis C virus (HCV) infections in the Han population. MATERIALS AND METHODS: The genotypes of TLR7IVS2-151 in HCV infection were detected by Sanger sequencing using polymerase chain reaction-restriction fragment length polymorphism to determine the TLR9 T-1486C single nucleotide polymorphisms (SNP) for all enrolled patients. RESULTS: We found no significant difference between males with spontaneous clearance of HCV versus those chronically infected [χ²=2.71, p=0.10, odd ratios (OR)=0.58, 95% confidence interval (CI) 0.31-1.11]. However, significant differences were found for the distribution of TLR7 (rs179009) in females (χ²=9.46, p=0.01). In females, a significant difference was also found between chronic hepatitis C and those with spontaneous clearance of HCV in terms of TLR7 IVS2-151G/A allele frequencies (χ²=9.50, p=0.00, OR=0.46, 95% CI 0.28-0.75). In HCV-infected patients, no significant association was found between the frequency of TLR9 genotypes and alleles. CONCLUSION: The site of TLR7 IVS2-151 (rs179009) G/A may be a factor for susceptibility of chronic HCV in the female Han population. TLR9T-1486C (rs18084) SNP may not play a major role in HCV infection. However, individual risk profiles for HCV infection did vary by sex and this relationship should be further investigated.

The roles of a novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8, in patients with coronary atherosclerotic heart disease.

OBJECTIVE: Inflammation is now considered a main pathogenic factor in coronary atherosclerotic heart disease (CHD), and it has a positive correlation with plaque vulnerability. A novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8 (MFG-E8), has been reported as having prominent anti-inflammatory effects in sepsis. However, few studies have reported on the association between MFG-E8 and CHD. In the present study, we aimed to investigate the serum MFG-E8 concentrations in patients with different stages of CHD or without CHD. Then, we studied the associations among MFG-E8, Gensini score, and high-sensitivity C-reactive protein (hs-CRP) in Chinese patients with CHD to illustrate the role of MFG-E8 in CHD. METHODS: A total of 176 controls and 295 patients with CHD were selected for this study. To evaluate CHD severity, we calculated the Gensini score for all of the subjects. Serum levels of MFG-E8 were determined by an enzyme-linked immunosorbent assay (ELISA) kit; serum total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), triglyceride (TG), and hs-CRP were detected by an automatic biochemistry analyzer; and fibrinogen (FIB) was analyzed with an automatic coagulation analyzer. RESULTS: Compared with the controls, the CHD group had a lower level of MFG-E8 (673.20±112.34 ng/mL vs. 134.89±4.74 ng/mL, p<0.001). The level of serum MFG-E8 in the acute myocardial infarction group (118.07±10.10 ng/mL) was significantly less than that in the stable angina group (p=0.025). Further analysis showed that MFG-E8 had a negative association with the Gensini score and the hs-CRP level (r=-0.590, p<0.001; r=-0.105, p=0.022, respectively). In addition, multiple regression analysis of the association between MFG-E8 and the main cardiovascular risk factors in our cases showed that MFG-E8 had a negative association with hs-CRP and a positive association with LDL-c (all p<0.05). CONCLUSION: The serum level of MFG-E8 was negatively associated with the severity of coronary artery stenosis and the risk of clinical events. Thus, MFG-E8 has the potential to be a marker of vascular complications.

Palmitate induces H9c2 cell apoptosis by increasing reactive oxygen species generation and activation of the ERK1/2 signaling pathway.

Cardiac myocytes undergo apoptosis under conditions of high free fatty acid concentrations, including palmitate, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain unknown. The aim of the present study was to understand the role of reactive oxygen species (ROS) production and the extracellular signal­regulated kinase 1/2 (ERK1/2) signaling pathway in palmitate­induced apoptosis in H9c2 cells. H9c2 cells were exposed to palmitate for 12 h. The effect on the cell viability of H9c2 cells was evaluated using the 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT) assay and cell apoptosis was determined by Hoechst 33342 staining. Levels of intracellular ROS were determined using a peroxide­sensitive fluorescent probe, 2',7'­dichlorofluorescein diacetate. Protein expression was measured by western blot analysis. Following treatment with palmitate for 12 h, H9c2 cells apoptosis was demonstrated as increased brightly condensed chromatin or unclear fragments by staining with Hoechst 33342, which was associated with increasing levels of active caspase­3 and cleaved poly (ADP-ribose) polymerase (PARP). In this model of treatment with palmitate, H9c2 cell apoptosis correlated with increased levels of p53 and Bax expression and reduced levels of Bcl-2 expression. Palmitate­induced apoptosis was observed to increase levels of intracellular ROS production and p­ERK1/2 and decrease p­Akt significantly. Consistent with these results, palmitate­induced apoptosis was attenuated by the ERK1/2 inhibitor, U0126, through partial reduction of intracellular ROS generation. Collectively, these results indicate that palmitate­induced apoptosis in H9c2 cells is mediated by activation of the ERK1/2 signaling pathway and increased ROS generation.

Recessive protective effect of ADIPOQ rs1501299 on cardiovascular diseases with type 2 diabetes: a meta-analysis.

The association between a common variant of the ADIPOQ gene rs1501299 (+276G>T) and cardiovascular diseases (CVDs) outcomes has been reported with many studies. However, the evidence is insufficient for strong conclusions regarding CVDs and ADIPOQ rs15011299 (+276G>T). We performed a meta-analysis about the association between ADIPOQ rs1501299 (+276G>T) and CVDs risk using a predefined protocol, including 15 published studies with 5868 cases and 10,744 controls. The pooled data suggested a recessive protective effect of ADIPOQ rs1501299 (+276G>T) on CVDs for type 2 diabetes (T2D) population: the TT homozygote individuals had a reduced risk of developing CVDs compared to the carriers of G allele (OR=0.74, 95% confidence interval (CI): 0.58, 0.94; p=0.013). But there is still not enough evidence to indicate the association of the ADIPOQ rs1501299 (+276G>T) and the development of cardiovascular diseases (CVDs) outcomes in general population. In conclusion, our meta-analysis suggested that the ADIPOQ rs1501299 (+276G>T) polymorphism is a low-risk factor for the development of CVDs with T2D, but the association of this polymorphism with the susceptibility to CVDs in other populations remains unknown. It could be presumed that the ADIPOQ rs1501299 (+276G>T) be a potential cause of susceptibility to CVDs in persons with T2D, and it gives a new opportunity to investigate the mechanisms of CVDs susceptibility in T2D patients.

Role of endogenous estrogen on the incidence of coronary heart disease in men.

Estrogens protect the vascular system in women, but its effect in men is unclear. We evaluated the impact of estrogen on the male cardiovascular system. Of 140 Chinese males, 55 (aged 61.2 ± 3.5) were cases and 60 (aged 59.5 ± 4.6) were controls. Compared with the control group, only serum estradiol ([E2]; P < .01) levels but not testosterone ([T]; P = .21) were significantly lower in the cases. Linear and multiple regression analysis showed that serum T was positively associated with triglycerides ([TG]; r = .439, P < .01) and d-dimer (r = .258, P < .05) but negatively associated with high-density lipoprotein cholesterol (HDL-C) levels (r = -.267, P < .05) and C-reactive protein (CRP; r = -.214, P < .05). Estradiol was highly associated with TG (r = .783, P < .01) and HDL-C (r = .515, P < .01) but was negatively related with low-density lipoprotein cholesterol (LDL-C; P < .05), total cholesterol/HDL-C (P < .05), CRP (P < .01), and d-dimer (P < .01). In conclusion, serum E2 and T levels affect coronary heart disease risk factors in males.

Imbalance of testosterone/estradiol promotes male CHD development.

OBJECTIVE: Testosterone is either neutral or has a harmful effect on the male cardiovascular system. But the role of imbalance of testosterone (T) and estrogen (E2) (T/E2 ratio) in male CHD has been less studied. This study was carried out with the purpose of evaluating the relationship between T/E2 ratio and CHD. METHODS: Fifty-five male CHD patients (aged 61.25 ± 3.44) and 60 age-matched controls (aged 59.54 ± 1.44) were selected in this research. RESULTS: Compared with control group, levels of both serum T and E2 decreased, but only E2 had statistical significance (P=0.001). The normal testosterone (T)/estradiol (E2) ratio is 1.7 ± 0.12, but the ratio of T/E2 (3.28 ± 0.58) changed significantly in men with CHD group (P<0.05). With the imbalance of T/E2 ratio in CHD group, we further used a linear and multiple regression methods to analyze the correlation between sex hormones and CHD risk factors. The results showed serum T was positively associated with TG (r=0.439, P<0.01) and D-dimer (r=0.258, P<0.05), but negatively associated with HDL-C (r=-0.267, P<0.05) and Hs-CRP (r=-0.214, P<0.05). However, E2 was highly positive associated with TG (r=0.783, P<0.01) and HDL-C (r=0.515, P<0.01), but was negative related with LDL-C (r=-0.219, P<0.05), TC/LDL (r=-0.236, P<0.05) and D-dimer. Multiple linear regression method also showed the same results between E2 and HDL-C (P=0.020), LDL-C (P=0.000), which showed E2's protective role in cases. However, T/E2's effect is more significative than E2's, and the values between T/E2 and index are HDL-C (r=-0.624, P<0.01), LDL-C (r=0.348, P<0.01), TC/HDL (r=0.237, P<0.05), Hs-CRP (r=0.248, P<0.05) and D-dimer (r=0.249, P<0.05). Multiple linear regression method also showed the positive relationship between T/E2 and HDL-C (P=0.000), D-dimer (P=0.000), and negative relationships between T/E2 and TC (P=0.000), TG (P=0.000) or HDL/LDL (P=0.000). CONCLUSION: The balance of T/E2 ratio, rather than the absolute levels of androgens, is crucial in modulating the effect of androgens on CHD in males.