Polymorphisms of CD247 gene is associated with dilated cardiomyopathy in Chinese Han population.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and heart transplantation. Recently, some studies have reported that the autoimmune response in myocardial cells might be related to the pathogenesis of DCM. The CD247 gene has been previously found to be involved in autoimmune disease. Therefore, our study aimed to clarify the hypothesis that there is a certain linkage between polymorphisms of the CD247 gene and the triggering of DCM risk. METHODS: In the present study, two single nucleotide polymorphisms (SNPs) of the CD247 gene, rs12141731 and rs858543, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 355 DCM patients and 404 age- and sex-matched controls. RESULTS: Pearson's chi-squared test for the CD247 gene revealed that SNP rs858543 (p = 0.001, OR = 0.72, 95% CI = (0.588-0.882), but not SNP rs12141731, was associated with DCM in the Chinese Han population. Haplotype analysis revealed that the CC haplotype was associated with increased DCM susceptibility, while CT was a protective haplotype. Cox multivariate survival analysis indicated that the rs858543 TT genotype (HR: 0.608, 95% CI = 0.402-0.921, p = 0.019) was an independent multivariate predictor for longer overall survival in DCM patients. CD247 mRNA expression levels were significantly decreased in DCM patients (p = 0.02). CONCLUSIONS: Our study suggested that a polymorphism in the CD247 gene may be a risk factor for DCM in the Chinese Han population. TRIAL REGISTRATION: ChiCTR2000029701.

A Bioequivalence Study of Ezetimibe/Rosuvastatin Fixed Dose Combination (10 mg/10 mg) Versus the Individual Formulations Taken Concomitantly.

INTRODUCTION: This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions. METHODS: This was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. Cmax, AUC0-t, and AUC0-∞ from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters. RESULTS: Of the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on Cmax, AUC0-t, and AUC0-∞ was similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng·h/mL, and 120 ng·h/mL for test formulation and 12.7 ng/ml, 120 ng·h/mL, and 123 ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for the test formulation and 3.80 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5 ng/ml, 664 ng·h/mL, and 718 ng·h/mL for test formulation and 60.2 ng/ml, 648 ng·h/mL, and 702 ng·h/mL for reference formulations. The point estimates for rosuvastatin unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80-1.25. No deaths or serious adverse events were reported. CONCLUSIONS: Fixed dose combination of ezetimibe/rosuvastatin (10 mg/10 mg) achieved bioequivalence with reference to commercial tablets. TRIAL REGISTRATION NUMBER: CTR20202108.

Pharmacokinetic Interactions and Tolerability of Rosuvastatin and Ezetimibe: A Randomized, Phase 1, Crossover Study in Healthy Chinese Participants.

BACKGROUND AND OBJECTIVE: The combination of rosuvastatin and ezetimibe has promising clinical benefits with a significant safety and tolerability profile. However, there is a lack of clinical data supporting the drug-drug interaction (DDI) in Chinese population. Thus, the aim of this study is to assess the potential pharmacokinetic DDI between rosuvastatin and ezetimibe in a Chinese population. METHODS: In this randomized, open-label, phase 1 study, 12 healthy volunteers were randomized to three treatment groups: 10 mg rosuvastatin plus 10 mg ezetimibe, 10 mg rosuvastatin alone, and 10 mg ezetimibe alone under fasting conditions. The plasma concentrations of rosuvastatin and ezetimibe were determined, and the pharmacokinetic parameters were calculated. Primary endpoints were peak plasma concentration (Cmax), area under the curve from zero to last measurement (AUC0-t), and area under the curve from zero to infinity (AUC0-∞) that were log-transformed, and co-administration was compared with monotherapy to evaluate the DDI. RESULTS: The geometric mean ratios (GMRs) of rosuvastatin with 90% confidence intervals (CIs) were 0.94 (0.80-1.12) for Cmax, 0.96 (0.85-1.08) for AUC0-t, and 0.96 (0.86-1.07) for AUC0-∞ when administered in combination with ezetimibe versus administered alone. The GMRs of unconjugated ezetimibe and total ezetimibe with 90% CIs were 1.15 (1.00-1.32) and 0.93 (0.80-1.07) for Cmax, 0.96 (0.84-1.10) and 0.95 (0.83-1.08) for AUC0-t, and 1.06 (0.96-1.18) and 0.94 (0.80-1.11) for AUC0-∞, respectively, when administered in combination with rosuvastatin versus administered alone. CONCLUSION: Co-administration of rosuvastatin and ezetimibe showed no clinically significant pharmacokinetic interactions in a healthy Chinese population.

[Association of OSMR gene polymorphisms with dilated cardiomyopathy in a Han Chinese population].

OBJECTIVE: To assess the association of polymorphisms of oncostatin M receptor (OSMR) gene with dilated cardiomyopathy (DCM) in a Han Chinese population. METHODS: For 351 DCM patients and 418 healthy controls, two single nucleotide polymorphisms (SNPs) of the OSMR gene, namely rs2292016 (promoter, -100G/T) and rs2278329 (missense, Asp553Asn), were genotyped with a TaqMan SNP genotyping assay. Two hundred of the patients were also followed up for (49.85 ± 22.52) months. RESULTS: For rs2292016, carriers of GT genotype were more likely to develop DCM compared to those with GG and TT genotypes (OR=1.45, 95%CI: 1.09-1.92, P=0.01). For those who did not receive cardiac resynchronization therapy, the GG genotype of rs2292016 was an independent indicator for poor prognosis (OR=1.69, 95%CI: 1.11-2.63, P=0.017). No association was found between genotypes of rs2278329 with the susceptibility or prognosis of DCM. CONCLUSION: Polymorphisms of the OSMR rs2292016 locus are related to the development and outcome of DCM.

Serum ω-3 Polyunsaturated Fatty Acids and Potential Influence Factors in Elderly Patients with Multiple Cardiovascular Risk Factors.

Recent clinical trials failed to demonstrate that ω-3 polyunsaturated fatty acid (PUFA) supplement reduced cardiovascular events, which contradicted previous evidence. However, serum ω-3 PUFA concentrations of participants remained unclear in those studies. We aimed to investigate the definite relationship between serum concentrations of ω-3 PUFAs and coronary artery disease (CAD), and to explore the potential influence factors of ω-3 PUFAs. We selected Chinese in-patients (n = 460) with multiple cardiovascular risk factors or an established diagnosis of CAD. Serum ω-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were measured by liquid chromatography mass spectrometry. Serum concentrations of ω-3 PUFAs in CAD patients were lower than that in patients with cardiovascular risk factors. Furthermore, high serum DHA concentration was an independent protective factor of CAD after adjustment for confounding factors (OR: 0.52, p = 0.014). Alcohol intake (p = 0.036) and proton pump inhibitor (PPI) usage (p = 0.027) were associated with a decreased serum ω-3 PUFA concentration. We conclude that serum concentrations of ω-3 PUFAs may associate with a decreased CAD proportion, and DHA may serve as a protective factor of CAD. Serum ω-3 PUFA concentrations may be reduced by alcohol intake and certain drugs like PPIs.

Single-nucleotide polymorphisms of the IL-12 gene lead to a higher cancer risk: a meta-analysis based on 22,670 subjects.

The associations between interleukin-12 (IL-12) gene polymorphisms and cancer risk have been discussed extensively, with controversial results. Therefore, we conducted the present meta-analysis to better assess the potential roles of IL-12 gene variation in cancer occurrence. Eligible articles were found via PubMed, Medline, EMBASE, Google Scholar and CNKI. Odds ratios and 95% confidence intervals were used to evaluate the associations between IL-12 gene polymorphisms and cancer risk. Thirty-one studies with 10,749 cancer patients and 11,921 healthy subjects were included in the analyses. The overall results showed that cancer risk was increased by IL-12A rs568408 (GG versus GA + AA: P = 0.004; G versus A: P = 0.005) and IL-12B rs3212227 (AA versus AC + CC: P = 0.004; CC versus AA + AC: P = 0.03; A versus C: P = 0.007) polymorphisms. Further subgroup analyses for IL-12A rs568408 and IL-12B rs3212227 revealed that the positive results could be impacted by the ethnicity of the population, cancer type and/or genotyping methods. However, we failed to detect any significant associations between the IL-12A rs2243115 polymorphism and cancer risk in either the overall or the subgroup analyses. The current study suggests that certain IL-12 gene polymorphisms serve as biological markers of cancer susceptibility.

The Roles of Genetic Factors in Kawasaki Disease: A Systematic Review and Meta-analysis of Genetic Association Studies.

This systematic review and meta-analysis aimed to better elucidate the roles of genetic factors in Kawasaki disease (KD), and determine the potential genetic biomarkers of KD. The systematic literature search of PubMed, Medline, Embase, Web of Science and CNKI identified 164 eligible studies. The qualitative synthesis revealed that 62 genes may be correlated with the susceptibility to KD, and 47 genes may be associated with the incidence of coronary artery lesions (CALs) in KD. A total of 53 polymorphisms in 34 genes were investigated in further quantitative synthesis. Of these, 23 gene polymorphisms were found to be significantly correlated with KD susceptibility, and 10 gene polymorphisms were found to be significantly associated with the incidence of CALs in KD. In conclusion, our findings indicate that gene polymorphisms of ACE, BLK, CASP3, CD40, FCGR2A, FGß, HLA-E, IL1A, IL6, ITPKC, LTA, MPO, PD1, SMAD3, CCL17 and TNF may affect KD susceptibility. Besides, genetic variations in BTNL2, CASP3, FCGR2A, FGF23, FGß, GRIN3A, HLA-E, IL10, ITPKC and TGFBR2 may serve as biomarkers of CALs in KD.

Human umbilical cord stem cell conditioned medium versus serum-free culture medium in the treatment of cryopreserved human ovarian tissues in in-vitro culture: a randomized controlled trial.

BACKGROUND: To reduce young female fertility loss, the in-vitro culture of cryopreserved ovarian cortical tissues (OCTs) is considered an effective approach without delaying treatment and undergoing stimulation medicine. However, ischemic damage and follicular loss during the in-vitro culture of OCTs are major technical challenges. Human umbilical cord stem cells (HUMSCs) and their conditioned medium (HUMSC-CM) have been considered to be potential resources for regeneration medicine because they secrete cytokines and enhance cell survival and function. The aim of this study was to determine whether HUMSC-CM improves the development of frozen-thawed in-vitro cultured ovarian tissues compared with a serum-free culture medium (SF-CM). METHODS: The thawed OCTs (n = 68) were cultivated in HUMSC-CM and SF-CM in vitro for 8 days, and the ovarian tissues were processed and analyzed by a classical histological evaluation. The microvessel density (MVD) and apotosis detection during in-vitro culture of OCTs were also performed. RESULTS: A significant difference in the rate of morphologically normal primordial follicles in the HUMSC-CM group was observed compared to that in the SF-CM group (group C) from days 2 to 4 (day 2: group B 58.0 ± 2.45% vs group C 32.0 ± 5.83%, p = 0.002; day 3: group B 55.5 ± 4.20% vs group C 21.0 ± 9.80%, p = 0.048; day 4: group B 52.0 ± 4.08% vs group C 21.5 ± 8.19%, p = 0.019). The microvessel density (MVD) detection showed a time-dependent increase and peaked on day 4. There was a significant difference between groups B (49.33 ± 0.58) and C (24.33 ± 3.79) (p = 0.036). The percentage of apoptotic follicles in group B was lower than that in group C on day 1 (13.75 ± 2.50% vs 27.0 ± 10.10%, p = 0.003), day 5 (11.75 ± 1.50% vs 51.0 ± 10.5%, p = 0.019) and day 7 (15.0 ± 5.10% vs 46.5 ± 21.75%, p = 0.018). CONCLUSIONS: These data have provided the first experimental evidence of the effect of HUMSC-CM on frozen-thawed OCTs in vitro. The results showed that the HUMSC-CM group provided a better protecting effect on the in-vitro culture of the cryopreserved OCTs compared to the SF-CM group.

Associations of common IL-4 gene polymorphisms with cancer risk: A meta-analysis.

Cancer incidence is dramatically increasing worldwide, therefore improved prediction and therapeutic methods are needed. Single nucleotide polymorphisms in cytokine genes may contribute to carcinogenesis. Interleukin (IL)­4 gene polymorphisms have been intensively studied with regard to their associations with cancer. However, the results of these previous studies remain inconclusive. The present study, therefore, aimed to conduct a meta­analysis of previously published studies in order to clarify the association of IL­4 with cancer risk. Eligible published articles were searched in Medline, PubMed, Embase and China National Knowledge Infrastructure databases up to March 2016. Odds ratios and 95% confidence intervals were used to identify potential associations between IL­4 genetic polymorphisms and the risk of cancer. A meta­analysis was then performed on 10,873 patients and 14,328 controls for IL­4 rs2243250 polymorphism, 3,970 patients and 5,686 controls for IL­4 rs2070874 polymorphism, and 1,896 patients and 2,526 controls for IL­4 rs79071878 polymorphism. A significant association with cancer risk was observed for rs2243250 and rs79071878 polymorphisms. In the subgroup analysis by cancer type, rs2243250 polymorphism was demonstrated to be associated with an increased risk of gastric cancer and breast cancer, rs2070874 polymorphism was correlated with leukemia and oral carcinoma, and rs79071878 polymorphism was relevant to bladder carcinoma risk. In the subgroup analysis by ethnicity, IL­4 rs2243250 polymorphism was demonstrated to be associated with cancer risk in both Caucasian and Asian populations, rs2070874 was associated with cancer risk in Asian populations, while rs79071878 polymorphism was associated with cancer risk in Caucasian populations. In conclusion, the present results suggested that the IL­4 rs2243250 and rs79071878 polymorphisms were associated with cancer susceptibility. Further subgroup analyses revealed that the effects of IL­4 gene polymorphisms on cancer risk may vary by cancer type and by ethnicity.

Associations between Interleukin-31 Gene Polymorphisms and Dilated Cardiomyopathy in a Chinese Population.

To explore the role of Interkeulin-31 (IL-31) in dilated cardiomyopathy (DCM), in our study, two SNPs of IL-31, rs4758680 (C/A) and rs7977932 (C/G), were analyzed in 331 DCM patients and 493 controls in a Chinese Han population. The frequencies of C allele and CC genotype of rs4758680 were significantly increased in DCM patients (P = 0.005, P = 0.001, resp.). Compared to CC genotype of rs4758680, the A carriers (CA/AA genotypes) were the protect factors in DCM susceptibility while the frequencies of CA/AA genotypes were decreased in the dominant model for DCM group (P < 0.001, OR = 0.56, 95%CI = 0.39-0.79). Moreover, IL-31 mRNA expression level of white blood cells was increased in DCM patients (0.072 (0.044-0.144) versus 0.036 (0.020-0.052), P < 0.001). In survival analysis of 159 DCM patients, Kaplan-Meier curve revealed the correlation between CC homozygote of rs4758680 and worse prognosis for DCM group (P = 0.005). Compared to CC genotype, the CA/AA genotypes were the independent factors in both univariate (HR = 0.530, 95%CI = 0.337-0.834, P = 0.006) and multivariate analyses after age, gender, left ventricular end-diastolic diameter, and left ventricular ejection fraction adjusted (HR = 0.548, 95%CI = 0.345-0.869, P = 0.011). Thus, we concluded that IL-31 gene polymorphisms were tightly associated with DCM susceptibility and contributed to worse prognosis in DCM patients.

Associations of TIM-1 Genetic Polymorphisms with Asthma: A Meta-analysis.

PURPOSE: Recently, the roles of TIM-1 genetic polymorphisms in asthma have been extensively studied, with conflicting results. Therefore, we performed the present meta-analysis to better assess potential associations of TIM-1 genetic polymorphisms with asthma. METHODS: Eligible articles were searched in PubMed, Medline, EMBASE, Google Scholar, and CNKI up to December 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between TIM-1 genetic polymorphisms and asthma. RESULTS: A total of 12 articles including 3120 asthma patients and 2825 control subjects were analyzed. The overall and subgroup analyses revealed that TIM-1-416G>C single nucleotide polymorphism was significantly associated with asthma for the Asian population in the codominant (G/G vs. G/C, p = 0.0003, OR 1.86, 95% CI 1.33-2.60) and dominant (G/G vs. G/C + C/C, p < 0.0001, OR 1.94, 95% CI 1.40-2.69) genetic models. Nevertheless, we failed to detect any significant associations between TIM-1-416G>C single nucleotide polymorphism and asthma in Caucasians. Additionally, according to our analyses, TIM-1 5383_5397 insertion/deletion polymorphism was not correlated with asthma in both Asians and Caucasians. CONCLUSIONS: In conclusion, our findings suggest that TIM-1-416G>C single nucleotide polymorphism is associated with asthma susceptibility for the Asian ethnicity in certain genetic models. However, TIM-1 5383_5397 insertion/deletion polymorphism may not be correlated with the risk of asthma.

Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects.

The endothelial nitric oxide synthase (eNOS) gene plays an important role in regulating vascular tone and blood pressure. Recently, the eNOS G894T and T-786C single nucleotide polymorphisms (SNPs) were intensively studied with regard to their associations with hypertension. However, the results of these studies were inconsistent. Therefore, we conducted the so far largest meta-analysis to better assess the correlations between eNOS SNPs and hypertension. Eligible articles were searched in PubMed, Medline, Embase, Scopus, and CNKI up to April 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between eNOS SNPs and the risk of hypertension. A total of 95 case-control studies involving 29,308 hypertension cases and 33,950 healthy controls were analyzed. The overall meta-analysis results showed that eNOS G894T and T-786C SNPs were both significantly associated with the risk of hypertension, the T allele of G894T SNP (G versus T, P < 0.00001, OR = 0.82, 95% CI 0.76-0.89) and C allele of T-786C SNP (T versus C, P = 0.004, OR = 0.92, 95% CI 0.87-0.97) conferred an increased susceptibility to hypertension. Further subgroup analyses yielded similar positive results for G894T SNP in essential hypertension, gestational hypertension, and Asian ethnicity, and that for T-786C SNP in essential hypertension and Asian population. Overall, our findings suggest that eNOS G894T and T-786C SNPs were both significantly correlated with hypertension. Additionally, the T allele of G894T SNP and C allele of T-786C SNP may serve as potential biological markers for hypertension susceptibility in Asians.

Associations of IL-10 genetic polymorphisms with the risk of urologic cancer: a meta-analysis based on 18,415 subjects.

BACKGROUND: Interleukin-10 (IL-10) is a powerful modulator of anti-tumor immune responses. The IL-10 promoter region polymorphisms are known to regulate IL-10 production, and thus are thought to be implicated in tumorigenesis. Recently, the roles of these polymorphisms in urologic cancer have been extensively studied, with conflicting results. Therefore, we conducted the present meta-analysis to better elucidate the correlations between IL-10 polymorphisms and urologic cancer risk. METHODS: Eligible articles were searched in PubMed, Medline, Embase, Scopus and CNKI up to May 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between IL-10 polymorphisms and the risk of urologic cancer. RESULTS: A total of 22 case-control studies including 8572 patients and 9843 controls were analyzed. The overall meta-analysis results showed that IL-10 -592C>A polymorphism was significantly associated with urologic cancer in CA versus AA (P = 0.04, OR 0.87, 95% CI 0.76-0.99) and AA versus CC+CA (P = 0.03, OR 1.15, 95% CI 1.02-1.31). Subgroup analyses by cancer types suggested there were significant associations between all the three investigated IL-10 polymorphisms and bladder cancer. However, subgroup analyses by ethnicity only detected a weak association between IL-10 -819C>T and Asian population. CONCLUSIONS: Our findings suggests that IL-10 -592C>A polymorphism may implicate with urologic cancer risk. Besides, promoter region polymorphisms of IL-10 may serve as potential biological markers, especially for bladder cancer. Furthermore, IL-10 -819C>T polymorphism may contribute to urologic cancer susceptibility in Asians while all the three studied variants of IL-10 did not relate to Caucasian urologic cancer predisposition.

Associations Between TIM1 Polymorphisms and Dilated Cardiomyopathy in a Han Chinese Population.

Immune dysfunction is implicated in dilated cardiomyopathy (DCM). Previous studies found that TIM1 polymorphisms were associated with immune dysfunction. However, the associations between TIM1 polymorphisms and DCM have not been investigated. Therefore, we conducted the present study to evaluate whether TIM1 polymorphisms were associated with DCM in the Han Chinese population. A total of 396 DCM patients and 403 healthy controls were enrolled in this case-control study. Two promoter region single nucleotide polymorphisms (SNPs) of TIM1 gene, -416G>C and -1454G>A, were genotyped by PCR-RFLP. The associations between two SNPs genotyped and the overall survival (OS) of DCM patients were evaluated with Kaplan-Meier analysis and Cox regression analysis. Plasma TIM-1 levels were further measured by ELISA. We found that the C allelic frequency of -416G>C and A allelic frequency of -1454G>A were higher in DCM patients than that in controls (P < 0.001). The genotypic frequencies of both SNPs were associated with DCM susceptibility in the codominant, dominant, and overdominant models (P < 0.01). They were also associated with the OS of DCM patients in the dominant, recessive, and overdominant models (P < 0.001). The CC genotype of -416G>C and AA genotype of -1454G>A were associated with the worst prognosis (P < 0.001). In addition, the plasma TIM-1 levels in DCM patients were higher than that in controls (259.0 pg/mL versus 149.8 pg/mL, P = 0.035). The CC genotype of 416G>C and AA genotype of -1454G>A were associated with the highest TIM-1 production (P < 0.01). Overall, our findings suggest that TIM1 polymorphisms are associated with DCM susceptibility and prognosis in this Han Chinese population.

Efficacy and Safety of Transcatheter Aortic Valve Implantation for Bicuspid Aortic Valves: A Systematic Review and Meta-Analysis.

PURPOSE: To elucidate the performance of transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BAV) patients through a systematic review and meta-analysis. METHODS: A systematic literature review was performed by searching eligible articles in PubMed, Medline, EMBASE, Google Scholar and CNKI. Meta-analysis of included case-control/cohort studies was further conducted. Relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were used to compare clinical outcomes of BAV patients and non-BAV patients. RESULTS: A total of 17 articles including eight case reports, four case series and five case-control/cohort studies with 166 BAV patients were analyzed. Device success rate achieved for TAVI in this cohort of BAV patients was 95.2%. The 30-day mortality rate was 8.4%, and the medium-term (range from 6 months to 2 years) mortality rate reported was 17.9%. Overall, the performance of TAVI in BAV patients was comparable to that in non-BAV patients, as reported by the included case-control/cohort studies (30-day mortality rate: RR = 1.05, 95%CI 0.57-1.95, p = 0.87; Device success rate: RR = 1.00, 95%CI 0.95-1.05, p = 0.94; Incidence of moderate to severe paravalvular regurgitation: RR = 1.25, 95%CI 0.85-1.84, p = 0.25). CONCLUSION: The present study suggested that TAVI may be a feasible and safe treatment modality for BAV patients.

Associations of NKX2-5 Genetic Polymorphisms with the Risk of Congenital Heart Disease: A Meta-analysis.

The NKX2-5 gene is a vital regulator of cardiac formation and development. Recently, the roles of NKX2-5 63A>G polymorphism and 606G>C polymorphism in congenital heart disease (CHD) have been extensively studied, with conflicting results. The aim of the present study was to better elucidate the associations between NKX2-5 genetic polymorphisms and CHD risk through a meta-analysis. Eligible articles were searched in PubMed, MEDLINE, EMBASE, Google Scholar and CNKI up to December 2015. Odds ratios (ORs) and 95 % confidence intervals were used to detect any potential associations between NKX2-5 genetic polymorphisms and CHD risk. Heterogeneity between studies was assessed with Q test and I (2) statistic. Subgroup analysis and sensitivity analysis were performed to test the reliability and stability of the results, and funnel plots were applied to estimate publication bias. A total of 13 case-control studies including 2245 CHD patients and 1953 healthy controls were analyzed. The overall meta-analysis results showed that NKX2-5 63A>G polymorphism and 606G>C polymorphism were not significantly associated with CHD risk. Subgroup analysis was further performed for NKX2-5 63A>G polymorphism based on types of CHD and ethnicity of study population, and similar negative results were found in all subgroups. Our findings suggested that NKX2-5 63A>G polymorphism and 606G>C polymorphism may not be implicated in the pathogenesis of CHD.

Associations of insulin receptor and insulin receptor substrates genetic polymorphisms with polycystic ovary syndrome: A systematic review and meta-analysis.

AIM: Recently, the roles of insulin receptor (INSR) and insulin receptor substrate (IRS) polymorphisms in polycystic ovary syndrome (PCOS) have been extensively studied, with conflicting results. Therefore, we conducted the present systematic review and meta-analysis to better evaluate associations of INSR and IRS polymorphisms with PCOS. METHODS: We searched PubMed, Medline, EMBASE, Google Scholar and China National Knowledge Infrastructure for eligible articles up to December 2015. Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate associations of INSR and IRS polymorphisms with PCOS. RESULTS: A total of 28 articles including 2975 PCOS patients and 3011 control subjects were analyzed. The overall analyses and subgroup analyses revealed that IRS-1 Gly972Arg polymorphism was significantly associated with PCOS for the Caucasian population in GG versus GA (OR = 0.57, 95%CI 0.37-0.89), GG versus GA + AA (OR = 0.57, 95%CI 0.36-0.89), GA versus GG + AA (OR = 1.74, 95%CI 1.13-2.69) and G versus A (OR = 0.63 95%CI 0.43-0.92). Also, IRS-2 Gly1057Asp polymorphism was significantly associated with PCOS for the Asian ethnicity in GG versus GA (OR = 0.45, 95%CI 0.24-0.83), GG versus AA (OR = 0.32, 95%CI 0.19-0.53), GG versus GA + AA (OR = 0.35, 95%CI 0.21-0.57), AA versus GG + GA (OR = 2.14, 95%CI 1.43-3.20), and G versus A (OR = 0.43, 95%CI 0.32-0.58). However, we detected no significant association between INSR His 1058 C/T polymorphism and PCOS. CONCLUSION: Our findings suggest that IRS-1 Gly972Arg polymorphism is associated with PCOS in the Caucasian ethnicity, and IRS-2 Gly1057Asp polymorphism is correlated with PCOS in the Asian ethnicity. However, INSR His 1058 C/T polymorphism may not be implicated in PCOS. © 2016 Japan Society of Obstetrics and Gynecology.

[Clinicopathologic characteristics of basal cell carcinoma of the prostate: analysis of 5 cases and review of the literature].

OBJECTIVE: To investigate the histogenesis, clinicopathologic characteristics, pathologic diagnosis, differential diagnosis, treatment and prognosis of basal cell carcinoma of the Prostate (BCCP). METHODS: We conducted clinicopathologic analysis on the manifestations of 5 cases of BCCP by HE staining and immunohistochemistry and reviewed relevant literature. RESULTS: Microscopically, the tumor cells were small in volume with ovoid karyomegaly and mitosis, some arranged like a solid nest or with a cribriform appearance. The tumors displayed an invasive growth, with positive expressions of 34betaE12, P63 and Cytokeratin 14, and negative expressions of PSA and P504s. No recurrence and metastasis were found in these patients during over 12 months of follow-up after surgery. CONCLUSION: BCCP is a rare neoplasm different from prostate adenocarcinoma. Immunohistochemistry is indispensable in distinguishing this tumor from other types of prostatic carcinoma. Its biological behavior remains to be further studied. The best treatment option may be radical surgery combined with chemo-radiotherapy at the present time.