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Xiaobo Li,
Yue Qi, Yuqiong Li,
Shanshan Zhang,
Shujie Guo,
Shaoli Chu,
Pingjin Gao,
Dingliang Zhu,
Zhijun Wu,
Lin Lu,
Weifeng Shen,
Nan Jia,
Wenquan Niu
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ABSTRACT: BACKGROUND: -A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRAs) on cardiac remodeling so far is lacking. We aimed to evaluate the impact of MRAs on changes in cardiac structure and function of left ventricular dysfunction. METHODS AND RESULTS: -Articles were identified by searches of PubMed, EMBASE, Cochrane, ClinicalTrials.gov databases before June 2012, and by hand searches of reviews and relevant journals, and by contact with the authors. Qualified articles were randomized controlled trials. There were respectively 12, 4 and 3 qualified trials that randomized 572, 647 and 407 patients to spironolactone, canrenoate and eplerenone, and 531, 655 and 395 patients to placebo or active treatment, respectively. Overall, under MRA treatment there was improvement in left ventricular ejection fraction (LVEF) (weighted mean difference; 95% confidence interval; P: 2.97; 2.26 to 3.67; <0.0005), left ventricular end-systolic and end-diastolic volume index (LVESVI and LVEDVI: -5.64; -7.94 to -3.34; <0.0005 and -7.46; -11.63 to -3.3; <0.0005), serum amino-terminal peptide of pro-collagen type-III (PIIINP) (-1.12; -1.49 to -0.74; <0.0005) and B-type natriuretic peptide (BNP) (-67.06; -91.24 to -42.88; <0.0005), peak velocities of early mitral inflow (E) (-9.57; -12.98 to -6.17; <0.0005), and E wave deceleration time (DT) (7.08; 4.07 to 10.09; <0.0005). There was low probability of heterogeneity and publication bias. CONCLUSIONS: -Our findings demonstrate that MRA treatment may exert beneficial effects on the reversal of cardiac remodeling and improvement of left ventricular function.
Circulation Heart Failure 02/2013; · 6.29 Impact Factor
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ABSTRACT: The prevalence of lung cancer in China will be the world's highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese.
This study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions) method. Data were analyzed by R language and multifactor dimensionality reduction (MDR) software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002) and Arg399Gln (P = 0.017), and in allele distributions of Thr241Met (P = 0.005). Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR): 2.47; 95% confidence interval (95% CI): 1.48-4.13; P<0.001). For Thr241Met, significance persisted under allelic (OR = 1.63; 95% CI: 1.14-2.33; P = 0.005), additive (OR = 1.64; 95% CI: 1.16-2.32; P = 0.005) and dominant (OR = 1.67; 95% CI: 1.17-2.38; P = 0.004) models. However, common allele combinations were comparable in frequency between patients and controls. In interaction analysis, the overall best MDR model included Arg399Gln and Thr241Met polymorphisms, with a maximal testing accuracy of 63.18% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0175).
Our study significantly demonstrated an independent and synergistic contribution of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms to lung cancer susceptibility in northeastern Chinese.
PLoS ONE 01/2013; 8(2):e56213. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: and objective: Many studies have examined the association between the angiotensin II receptor, type 1 (AGTR1) gene A1166C polymorphism and coronary artery disease (CAD); the results, however, remain controversial. Given the accumulation of data, we conducted a meta-analysis of published studies on this association in Chinese. METHODS: and results: A comprehensive search of PubMed, Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases was conducted before January 2012. Data and study quality were assessed in duplicate. Twenty-two studies totaling 3502 CAD patients and 3071 controls were analyzed. Overall, individuals carrying 1166C allele had a remarkably increased risk of CAD compared with those with 1166AA genotype (odds ratio (OR)=1.63; 95% confidence interval (CI): 1.26-2.1; P<0.0005). In subgroup analyses by geography, the risk magnitude was slightly augmented in northern Chinese (OR=1.76; 95% CI: 1.23-2.52; P=0.002) relative to in southern Chinese (OR=1.55; 95% CI: 1.13-2.14; P=0.007). Grouping studies by average age detected a strong association in studies involving CAD patients aged ≥ 60 years. Differences in the diagnosis of CAD and source of controls might be potential sources of between-study heterogeneity. CONCLUSIONS: Our findings provided strong evidence that AGTR1 gene A1166C polymorphism might be a genetic marker for the development of CAD in Chinese populations, especially in the context of studies with northern and older subjects.
Journal of Renin-Angiotensin-Aldosterone System 07/2012; · 2.44 Impact Factor
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ABSTRACT: Large panels of studies have examined the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk for left ventricular hypertrophy (LVH), yet with inconclusive results. We therefore sought to evaluate this association via a comprehensive meta-analysis. A random-effects model was applied irrespective of between-study heterogeneity. Data and study quality were independently assessed by two investigators. Total 52 studies encompassing 3,663 case-patients and 8,953 controls were meta-analyzed. Overall results indicated that carriers homozygous for DD genotype conferred 1.59 times (95 % confidence interval [95 % CI]: 1.31-1.92; P < 0.0005) more likely to develop LVH compared with those with II genotype, accompanying moderate evidence of heterogeneity (I (2) = 49.0 %). In subgroup analyses by ethnicity, DD homozygotes had a 90 % (95 % CI: 1.42-2.53; P < 0.0005) increased risk in East Asians, but merely a 33 % (95 % CI: 1.03-1.73; P = 0.032) increased risk in Caucasians. Moreover, differences in source of controls, cutoff for the definition of hypertension, and diagnostic method of LVH were also regarded as potential sources of heterogeneity. Further, the risk estimate associated with D allele was more pronounced in studies involving males (odds ratio [OR] = 1.47; 95 % CI: 1.2-1.8; P < 0.0005) and untreated subjects (OR = 1.39; 95 % CI: 1.2-1.62; P < 0.0005). The magnitude of publication bias was greatly improved in homozygous subgroups. Taken together, our results demonstrated significant association of ACE gene I/D polymorphism with LVH risk, especially in East Asians, and this association was more pronounced in studies involving males and untreated subjects.
Molecular Biology Reports 07/2012; · 2.93 Impact Factor
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ABSTRACT: Lung cancer is the most common cause of cancer-related deaths worldwide. The aim of this study was to investigate the association of five extensively-studied polymorphisms in PTGS2 (rs689466, rs5275, rs20417) and CYP2E1 (rs2031920, rs6413432) genes with lung cancer risk in a large northeastern Chinese population.
This is a hospital-based case-control study involving 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR method. Data were analyzed using Haplo.stats and MDR programs. There were significant differences between patients and controls in allele/genotype distributions of rs5275 (P = 0.002/0.003) and rs6413432 (P = 0.037/0.044), as well as in genotype distributions of rs689466 (P = 0.02). The risk for lung cancer associated with the rs5275-C mutant allele was decreased by 60% (95% CI [confidence interval]: 0.21-0.74; P = 0.004) under the recessive model. Carriers of rs689466-G mutant allele had a 28% (95% CI: 0.57-0.92; P = 0.008) reduced risk of developing lung cancer relative to the AA genotype carriers. In haplotype analysis, haplotype G-C-C-T (in order of rs689466, rs5275, rs2031920 and rs6413432) decreased the odds of lung cancer by 28% (95% CI: 0.51-0.93; P = 0.019) after adjusting for confounding factors, whereas haplotype A-T-T-T had 1.49-fold (95% CI: 1.21-1.79; P = 0.012) increased risk for lung cancer. Using MDR method, the overall best model including rs5275, rs689466 and rs6413432 polymorphisms was identified with a maximal testing accuracy of 66.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.003).
Our findings demonstrated a potentially synergistic association of PTGS2 and CYP2E1 polymorphisms with the underlying cause of lung cancer in northeastern Chinese.
PLoS ONE 01/2012; 7(6):e39814. · 4.09 Impact Factor
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ABSTRACT: The association between NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue.
This case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions) method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR) = 0.99; 95% confidence interval (CI): 0.92-1.06; P = 0.692) and dominant (OR = 0.98; 95% CI: 0.89-1.08; P = 0.637) models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis.
Our study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations.
PLoS ONE 01/2012; 7(10):e47939. · 4.09 Impact Factor
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ABSTRACT: The hematopoietically-expressed homeobox (HHEX) gene is identified as a promising candidate for type 2 diabetes by genome-wide association studies, triggering plenty of subsequent replications; however, the results are conflicting. We therefore conducted a meta-analysis of three widely-evaluated polymorphisms in HHEX gene and diabetes risk.
A random-effects model was adopted irrespective of heterogeneity. Data and study quality were assessed in duplicate. There were 49 studies (cases/controls: 57931/74658) for rs1111875, 18 studies (18227/30366) for rs5015480 and 26 studies (25725/30579) for rs7923837, respectively. Overall analyses indicated that rs1111875-C allele (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.13-1.2; P<0.0005), rs5015480-C allele (OR = 1.16; 95% CI: 1.06-1.26; P = 0.001) and rs7923837-G allele (OR = 1.18; 95% CI: 1.12-1.24; P<0.0005) conferred significantly increased risk for type 2 diabetes, yet accompanying moderate to strong evidence of heterogeneity. Despite vast divergence in allele distributions, subgroup analyses by ethnicity showed comparable risk estimates between Asians and Caucasians for three examined polymorphisms. Moreover, results of studies with hospital-based controls deviated greatly from that of all qualified studies, especially for rs7923837-G allele carrying a doubled risk (OR = 1.37 versus 1.18). Furthermore, when only large studies (≥500 case-patients) were considered, risk effects were identical to the overall estimates for three examined polymorphisms. The Begg's funnel plot and Egger's test indicated low probability of publication bias.
Our results provide clarification to the significant association of rs1111875, rs5015480 and rs7923837 in HHEX gene with type 2 diabetes.
PLoS ONE 01/2012; 7(11):e49917. · 4.09 Impact Factor
