Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism and Cardiometabolic Risk Factors: A Study Among Bhil Tribal Population from Two Environmental Settings

Studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and cardiometabolic risk factors (CMRFs), however with varying results, which could be due to ethnicity differences. Therefore, the present study was conducted among Bhil tribal population (a mendelian population with the common gene pool and same sociocultural attributes), residing in two different environmental settings. The study attempts to understand the distribution and extent of association of ACE I/D gene polymorphism with cardiometabolic risk factors among Bhils from rural and urban settings. All the obesity and blood pressure variables were collected form 432 recruited subjects from both sexes aged 25–65 years and ACE I/D polymorphism was analysed on 299 subjects. Almost all the studied CMRFs were found to be significantly higher among urban Bhils. ACE gene was found to be polymorphic in the studied groups. DD genotype was found to pose more than threefold significant risk for low HDLC only in rural area. Estimate change analysis revealed an increasing D allele dose leads to more than one unit increase in Blood Pressure, and more than three units decrease in HDLC. The study highlights the differential effect of ACE I/D gene polymorphism in different environmental settings.     

Association between Angiotensin I-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of Kidney Transplantation: A Meta-Analysis

PurposeAngiotensin I-converting enzyme (ACE) is crucial in the renin–angiotensin–aldosterone system. ACE insertion/deletion (I/D) polymorphism is a common genetic variation of this gene and is associated with several disease phenotypes. However, the results of published studies on the influence of this polymorphism on renal transplantation are inconsistent. Therefore, a meta-analysis was performed to evaluate the association between ACE I/D polymorphism and prognosis of kidney transplantation.MethodsA meta-analysis was performed based on 21 case–control studies from 12 publications (1497 cases and 2029 controls) and 10 studies with quantitative values from 5 publications (814 patients). Pooled odds ratios (ORs) and weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were used to estimate associations.ResultsACE I/D polymorphism was found to be associated with acute rejection (AR) in genotypes DD+ID versus II (OR = 1.62, 95% CI = 1.14–2.29) and with serum creatinine concentration after renal transplantation in genotypes DD versus ID (WMD = 13.12, 95% CI = 8.09–18.16). Stratified analysis revealed that recipients transplanted within a year had higher serum creatinine concentrations in the DD versus ID model. No significant association was found between hypertension and ACE I/D polymorphism.ConclusionACE I/D polymorphism is associated with AR and allograft function after kidney transplantation.     

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Is Not a Major Determining Factor in the Development of Sporadic Alzheimer Disease: Evidence from an Updated Meta-Analysis

Angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism have long been linked to sporadic Alzheimer disease (SAD), but the established data remained controversial. To clarify this inconsistency, a comprehensive meta-analysis was conducted. Through searching of Pubmed, Embase, Alzgene, China National Knowledge Infrastructure (CNKI) and manually searching relevant references, 53 independent studies from 48 articles were included, involving a total of 8153 cases and 14932 controls. The strength of association was assessed by using odds ratios (ORs) with 95% confidence intervals (CIs). Further stratified analyses and heterogeneity analyses were tested, as was publication bias. Overall, significant associations were revealed between I/D polymorphism and SAD risk using allelic comparison (OR = 1.09, 95%CI = 1.01–1.17, p = 0.030), homozygote comparison (OR = 1.17, 95%CI = 1.01–1.34, p = 0.030) and the dominant model (OR = 1.16, 95%CI = 1.04–1.29, p = 0.008), but they were not sufficiently robust to withstand the false-positive report probability (FPRP) analyses. Otherwise, in subgroup analyses restricted to the high quality studies, the large sample size studies and studies with population-based controls, no significant association was observed in any genetic models. In summary, the current meta-analysis suggested that the ACE I/D polymorphism is unlikely to be a major determining factor in the development of SAD.     

Hsa-miR-499 rs3746444 Polymorphism Contributes to Cancer Risk: A Meta-Analysis of 12 Studies

Background

Single nucleotide polymorphisms (SNPs) occurred in pre-microRNAs or targets of microRNAs (miRs) may contribute to cancer risks. Since 2007, many studies have investigated the association between common SNPs located on hsa-miR-499 (rs3746444) and cancer risks; however, the results were inconclusive.

Methodology/Principal Findings

We conducted a meta-analysis of 12 studies that included 5765 cases and 7076 controls to identify the strength of association. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, individuals with the variant AG (OR = 1.215, 95% CI: 1.027, 1.437; P_{heterogeneity}<0.01) and AG/GG (OR = 1.227, 95% CI: 1.046, 1.439; P_{heterogeneity}<0.01) genotypes were associated with a significantly increased risk of cancer than those with wild AA genotype. Sub-group analysis revealed that the variant AG (OR = 1.411, 95% CI: 1.142, 1.745; P_{heterogeneity} = 0.01) and AG/GG (OR = 1.413, 95% CI: 1.163, 1.717, P_{heterogeneity} = 0.01) genotypes still showed an increased risk of cancer in Asians; however, a trend of reduced risk of cancer was observed in Caucasians (AG vs. AA: OR = 0.948, 955 CI: 0.851, 1.057, P_{heterogeneity} = 0.12; AG/GG vs. AA: OR = 0.959, 95% CI: 0.865, 1.064; P_{heterogeneity} = 0.19). Meta-regression showed that ethnicity (p = 0.048) and sample size (p = 0.02) but not cancer types (p = 0.89) or source of control (p = 0.97) were the sources of heterogeneity.

Conclusions

These meta-analysis results suggest that hsa-miR-499 polymorphism rs3746444 is associated with a significantly increased risk of cancer, especially in Asian populations.     

飞行员中血管紧张素转换酶基因插入或缺失多态性研究

为了解飞行员血管紧张素转换酶(ACE)基因插入或缺失（I/D）多态性情况,探讨ACE基因多态性与飞行员耐力可能的关系,用聚合酶链反应（PCR）扩增技术检测118例飞行员和96例健康对照者的ACE基因I/D多态性。 结果位于ACE基因内含子16的I/D多态性经PCR扩增后呈三种基因型：纯合子插入型（II）、纯合子缺失型（DD）和杂合子插入或缺失型（I/D）。飞行员组II基因型（44.07%）和I等位基因频率（0.65）显著高于健康对照组(分别为31.25%和0.52)。 结果表明ACE I基因有可能在飞行员的飞行耐力中起重要作用。 Abstract:In order to understand insertion/delation (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in pilots,and to explore the relationship between ACE gene I/D polymorphism and the perfomance of the pilots,the polymerase chain reaction (PCR) was used to determine the genotypes for an I/D polymorphism in intron 16 of the ACE gene in 118 pilots and 96 healthy subjects as controls.The result showed that the I/D polymorphism in intron 16 of the ACE gene was categorized into three genotypes: two deletion alleles (genotype DD),heterozygous alleles (genotype ID),and two insertion alleles (genotype II).The genotype II and I allele frequency were significantly higher in pilots (44.07% and 0.65) than that in healthy subjects (31.25% and 0.52).It is suggested that I gene of ACE may play a role in perfomance of the pilots.     

Insertion/Deletion Polymorphism and Serum Activity of the Angiotensin-Converting Enzyme in Turkish Patients with Obstructive Sleep Apnea Syndrome

This study determined the allelic frequency and genotypic distribution of an angiotensin-converting enzyme (ACE) polymorphism and serum ACE activity in Turkish patients with obstructive sleep apnea syndrome (OSAS). A colorimetric assay measured serum ACE activity in 73 of 97 subjects. Frequencies for II, ID, and DD genotypes were 19.6, 53.6, and 26.8% in the OSAS group and 15, 38, and 47% in the control group, respectively (P = 0.02). The I allele frequency was higher in the OSAS group than in the healthy control group (P = 0.02). Carrying the I allele (II or ID genotypes) increased OSAS risk 2.41 times in the Turkish population. Mean ACE activity was significantly lower in patients with the II genotype than in the DD genotype (P = 0.011), and ACE activity was significantly lower in patients with severe OSAS than in those with mild OSAS (P = 0.006). Our results suggest that II and ID genotypes of the ACE gene increase the risk of developing OSAS in the Turkish population.     

The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

Objective

A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.

Methods

Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.

Results

Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.

Conclusion

The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.     

The -607C/A Polymorphisms in Interleukin-18 Gene Promoter Contributes to Cancer Risk: Evidence from A Meta-Analysis of 22 Case-Control Studies

Background

Several observational studies have investigated the association between -607 C/A polymorphism of IL-18 gene and cancer risk; however, the results were inconsistent. Therefore, we performed a meta-analysis to derive a more precise estimation of the association to help us better understand the relationship between -607 C/A polymorphism of IL-18 gene promoter and risk of cancer.

Methods

A literature search was carried out using PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database between January 1966 and February 2013. Fixed-effect and random-effect models were used to estimate the pooled odds ratio (OR) and the corresponding 95% confidence intervals (CIs).

Results

A total of 22 case-control studies including 4100 cancer cases and 4327 controls contributed to the analysis. Significant association between -607C/A polymorphism in IL-18 gene promoter and cancer risk was observed (CA vs CC:OR =1.221, 95% CI: 1.096, 1.360; P_{heterogeneity}=0.219; AA/CA vs. CC:OR =1.203, 95% CI: 1.057, 1.369; P_{heterogeneity}=0.064). In the subgroup analysis by ethnicity, -607C/A polymorphism significantly increased risk of cancer among Asian population (AA/CA vs. CC:OR =1.197, 95% CI: 1.023,1.401; P_{heterogeneity}=0.088); however, no significant association was found in Caucasian or African population. The -607C/A polymorphism was associated with a significantly increased risk of nasopharyngeal carcinoma (CA vs CC:OR =1.330, 95% CI: 1.029,1.719; P_{heterogeneity}=0.704; AA/CA vs. CC:OR =1.323, 95% CI: 1.037,1.687; P_{heterogeneity}=0.823) and esophageal cancer (AA/CA vs. CC:OR =1.289, 95% CI: 1.002,1.658; P_{heterogeneity}=0.700).

Conclusions

The present meta-analysis suggests that the -607C/A polymorphisms in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially for nasopharyngeal carcinoma and esophageal cancer and in Asian population. More studies with larger sample size, well controlled confounding factors are warranted to validate this association.     

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study

BackgroundAutism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.MethodsConsidering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThere were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64–5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37–3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26–2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.     

Genetic Polymorphism in PDE4D Gene and Risk of Ischemic Stroke in Chinese Population: A Meta-Analysis

Background

Stroke is the second most common cause of death and major cause of disability worldwide. The SNP 83 in PDE4D gene has been suggested as a risk factor in ischemic stroke, but direct evidence from genetic association studies remains inconclusive even in Chinese population.

Methods

Meta-analysis of case-control studies on the relationship between SNP 83 in PDE4D gene and susceptibility to ischemic stroke in Chinese population published domestically and abroad from January 2003 to September 2012.

Results

9 case-control studies were selected. Meta-analysis results showed that the significant association between SNP 83 and ischemic stroke was found under the dominant model (OR = 1.34, 95% CI: 1.20–1.49) and recessive model (OR = 1.45, 95% CI: 1.19–1.76) in Chinese population. In subgroup meta-analysis, SNP 83 and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the dominant model (OR = 1.69, 95% CI: 1.41–2.01) and recessive model (OR = 1.47, 95% CI: 1.04–2.06).

Conclusions

The results suggest that SNP 83 in PDE4D gene is significantly associated with susceptibility to ischemic stroke in Chinese population.     

Sulfotransferase SULT1A1 Arg213His Polymorphism with Cancer Risk: A Meta-Analysis of 53 Case-Control Studies

Background

The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis.

Methods

Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).

Results

A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR = 1.09, 95% CI = 1.01–1.18, P = 0.040), dominant (OR = 1.10, 95% CI = 1.01–1.19, P = 0.021) and allelic (OR = 1.08, 95% CI = 1.02–1.16, P = 0.015) models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT) cancer (heterozygous model: OR = 1.62, 95% CI = 1.11–2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13–2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10–2.11, P = 0.012) and Indians (recessive model: OR = 1.93, 95% CI = 1.22–3.07, P = 0.005) subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected.

Conclusions

The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn''t show any association with breast cancer, but the possible risk in Asian population needs further investigation.     

Association between the Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Angiopathy in Patients with Non-Insulin Dependent Diabetes Mellitus in Chuvash Republic

Insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene was analyzed in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in the control group consisting of healthy subjects. The insertion allele (I) and genotype II were found to be associated with NIDDM. The frequencies of diabetic retinopathy and nephropathy in NIDDM patients were not associated with this polymorphism. However, an association was found between the DD genotype of the ACE gene and diabetic angiopathy in lower extremities.     

Three ADIPOR1 Polymorphisms and Cancer Risk: A Meta-Analysis of Case-Control Studies

Background

Studies have come to conflicting conclusions about whether polymorphisms in the adiponectin receptor 1 gene (ADIPOR1) are associated with cancer risk. To help resolve this question, we meta-analyzed case-control studies in the literature.

Methods

PubMed, EMBASE, Cochrane Library, the Chinese Biological Medical Database and the Chinese National Knowledge Infrastructure Database were systematically searched to identify all case-control studies published through February 2015 examining any ADIPOR1 polymorphisms and risk of any type of cancer. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated.

Results

A total of 13 case-control studies involving 5,750 cases and 6,762 controls were analyzed. Analysis of the entire study population revealed a significant association between rs1342387(G/A) and overall cancer risk using a homozygous model (OR 0.82, 95%CI 0.72 to 0.94), heterozygous model (OR 0.84, 95%CI 0.76 to 0.93), dominant model (OR 0.85, 95%CI 0.75 to 0.97) and allele contrast model (OR 0.88, 95%CI 0.80 to 0.97). However, subgroup analysis showed that this association was significant only for Asians in the case of colorectal cancer. No significant associations were found between rs12733285(C/T) or rs7539542(C/G) and cancer risk, either in analyses of the entire study population or in analyses of subgroups.

Conclusions

Our meta-analysis suggests that the ADIPOR1 rs1342387(G/A) polymorphism, but not rs12733285(C/T) or rs7539542(C/G), may be associated with cancer risk, especially risk of colorectal cancer in Asians. Large, well-designed studies are needed to verify our findings.     

The Glutathione S-Transferase P1 341C>T Polymorphism and Cancer Risk: A Meta-Analysis of 28 Case-Control Studies

Background

GSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted.

Methodology/Principal Findings

The relevant studies were identified through searching of PubMed, Embase, ISI Web of Knowledge and China National Knowledge Infrastructure in August 2012, and selected based on the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize the association of GSTP1 341C>T polymorphism with cancer susceptibility. Stratified analyses were employed to identify the source of heterogeneity. Publication bias was evaluated as well as sensitivity analysis. Based on 28 case-control studies with 13249 cases and 16798 controls, the pooled results indicated that the variant genotypes significantly increased the risk of cancer in homozygote comparison (TT versus CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, P _het. = 0.575), and recessive model (TT versus CT/CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, P _het. = 0.562). This was confirmed when stratified analyses were conducted according to ethnicity, source of control, matched control, quality score and cancer types. Moreover, significantly increased risk of cancer was also found in lung cancer (heterozygote comparison and dominant model). The stability of these observations was confirmed by a sensitivity analysis. Begger''s funnel plot and Egger''s test did not reveal any publication bias.

Conclusions/Significance

This meta-analysis suggests that the GSTP1 341C>T polymorphism may contribute to genetic susceptibility to cancer, especially to lung cancer, and in Asian population. Nevertheless, additional well-designed studies focusing on different ethnicity and cancer types are needed to provide a more exact and comprehensive conclusion.     

Association of GSTP1 Ile105Val Polymorphism and Risk of Head and Neck Cancers: A Meta-Analysis of 28 Case-Control Studies

Background and Aims

The Glutathione S-transferase P1 (GSTP1) polymorphism have been considered a risk modifier for developing head and neck cancer (HNC) in many studies; however, the results of such studies are inconsistent. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val polymorphism and risk of HNC.

Method

We performed a search in the relevant electronic database and a meta-analysis based on 28 published case–control studies that included 6,404 cases and 6,523 controls. To take into account the possibility of heterogeneity across the studies, a Chi-square based I²-statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using both fixed-effects and random-effects models.

Results

The results of this meta-analysis showed that the GSTP1 Ile105Val polymorphism was not significantly associated with risk of HNC in the overall study population (pooled OR 1.00, 95% CI 0.92–1.09) or in subgroup analyses stratified by ethnicity, sample size, tumor site or publication year. Moreover, substantial evidence of heterogeneity among the studies was observed. Publication year was identified as the main cause of heterogeneity.

Conclusion

This meta-analysis does not support a significant association between the GSTP1 Ile105Val polymorphism and risk of HNC.     

Association between Transforming Growth Factor-Beta 1 T869C Polymorphism and Ischemic Stroke: A Meta-Analysis

Objective

To explore the association between transforming growth factor-beta1 (TGF-β1) T869C polymorphism and risk of ischemic stroke (IS) by performing a meta-analysis based on published articles.

Methods

Systematic electronic searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANFANG Database were performed. The strength of the association was calculated by pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by Begg’s funnel plot and Egger’s test.

Results

A total of 6 studies involving 1701 cases were included. The overall estimates did not show any significant association between TGF-β1 T869C polymorphism and risk of IS under all genetic models (C vs. T: OR = 1.08,95%CI = 0.88–1.32; CC vs. TT:OR = 1.17,95%CI = 0.79–1.72; CT vs. TT: OR = 0.91, 95%CI = 0.68–1.22; CC+CT vs. TT: OR = 0.99, 95%CI = 0.73–1.35; CC vs. CT+TT: OR = 1.23, 95%CI = 0.95–1.59). Similar lacking associations were observed in subgroup analysis based on ethnicity and source of controls. When stratified by study design, significant increased association of IS risk was found in cohort studies under genetic models except recessive model(C vs. T: OR = 1.18, 95%CI = 1.05–1.32; CC vs. TT: OR = 1.40, 95%CI = 1.10–1.77; CT vs. TT: OR = 1.23, 95%CI = 1.02–1.49; CC+CT vs. TT: OR = 1.27, 95%CI = 1.03–1.57; CC vs. CT+TT, OR = 1.21, 95%CI = 0.99–1.47), whereas in case-control studies a significant decreased risk was detected under heterozygote comparison(CT vs. CC: OR = 0.72, 95%CI = 0.57–0.92). However, after correction for multiple testing, the associations were observed to be null significant in both cohort and case-control subgroups among all genetic models.

Conclusion

This meta-analysis suggested that current epidemiological studies of TGF-β1 T869C polymorphism are too inconsistent to draw a conclusion on the association with IS susceptibility. Given the small sample size and remarkable between-study heterogeneity, further well-designed prospective large-scale studies are warranted.     

Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis

Background

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Methods

We firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.

Results

The case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).

Conclusions

A significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.     

Genetic Polymorphisms of XRCC1 and Leukemia Risk: A Meta-Analysis of 19 Case-Control Studies

Objective

Three common X-ray repair cross-complementing groups 1 (XRCC1) polymorphisms, Arg399Gln, Arg194Trp, and Arg280His, have been reported to be implicated in the development of leukemia. However, previous results from different studies were inconsistent. Consequently, we performed a meta-analysis in order to accurately evaluate the association between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and leukemia risk.

Methods

Through computerized searching of PubMed, ISI Web of Knowledge, Cochrane, EBSCO, and OpenGrey databases, and manually searching relevant references, a total of 19 studies with 3387 cases and 6168 controls for Arg399Gln (G>A) polymorphism, 12 studies with 2043 cases and 4550 controls for Arg194Trp (C>T), and 6 studies with 1445 cases and 1905 controls for Arg280His (G>A) were collected to perform meta-analysis and stratified analysis to explore the associations between these variants and leukemia susceptibility. Based on three genetic models, the codominant model, dominant model and recessive model, odds ratios (ORs) as well as their 95% confidence intervals (CIs) were used to evaluate the association strength between XRCC1 genotypes and leukemia risk.

Results

With respect to overall leukemia susceptibility, no association was detected. In stratified analyses by tumor type, Arg399Gln was associated with higher acute lymphoblastic leukemia (ALL) risk (AA vs. GG, OR  =  1.50, 95% CI: 1.11-2.02; AA+GA vs. GG, OR  =  1.35, 95% CI: 1.02-1.78). Additionally, Arg399Gln, Arg194Trp, and Arg280His may influence the susceptibilities of some leukemia type and race populations.

Conclusion

This meta-analysis indicates these three polymorphisms of XRCC1 do not associate with overall leukemia risks but could be associated with the risks for some specific subgroups.     

Prevalence of the Angiotensin I Converting Enzyme Gene Insertion/Deletion Polymorphism in a Healthy Turkish Population

Angiotensin converting enzyme (ACE) plays an essential role in the renin–angiotensin system. It converts angiotensin I to angiotensin II and inactivates bradykinin and tachykinins. Numerous studies have been published investigating associations of the ACE gene I/D polymorphism with various pathophysiological conditions. We examined the prevalence of the ACE I/D polymorphism in a sample of healthy volunteers from western Turkey, including 1063 healthy Turkish controls. Analysis of the ACE I/D gene polymorphisms by polymerase chain reaction found frequencies of 16.1% for the II genotype, 47.7% for the ID genotype, and 36.2% for the DD genotype. The allele frequency was 39.9% for the I alleles and 60.1% for the D allele. This study demonstrates that the allele and genotype frequency values for the Turkish population are similar to previously published frequencies for Caucasian populations.     

Association between TGFBR1 Polymorphisms and Cancer Risk: A Meta-Analysis of 35 Case-Control Studies

Background

Numerous epidemiological studies have evaluated the association between TGFBR1 polymorphisms and the risk of cancer, however, the results remain inconclusive. To derive a more precise estimation of the relation, we conducted a comprehensive meta-analysis of all available case-control studies relating the TGFBR1*6A and IVS7+24G>A polymorphisms of the TGFBR1 gene to the risk of cancer.

Methods

Eligible studies were identified by search of electronic databases. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were applied to assess the associations between TGFBR1*6A and IVS7+24G>A polymorphisms and cancer risk.

Results

A total of 35 studies were identified, 32 with 19,767 cases and 18,516 controls for TGFBR1*6A polymorphism and 12 with 4,195 cases and 4,383 controls for IVS7+24G>A polymorphism. For TGFBR1*6A, significantly elevated cancer risk was found in all genetic models (dominant OR = 1.11, 95% CI = 1.04∼1.18; recessive: OR = 1.36, 95% CI = 1.11∼1.66; additive: OR = 1.13, 95% CI = 1.05∼1.20). In subgroup analysis based on cancer type, increased cancer risk was found in ovarian and breast cancer. For IVS7+24G>A, significant correlation with overall cancer risk (dominant: OR = 1.39, 95% CI = 1.15∼1.67; recessive: OR = 2.23, 95% CI = 1.26∼3.92; additive: OR = 1.43, 95% CI = 1.14∼1.80) was found, especially in Asian population. In the subgroup analysis stratified by cancer type, significant association was found in breast and colorectal cancer.

Conclusions

Our investigations demonstrate that TGFBR1*6A and IVS7+24G>A polymorphisms of TGFBR1 are associated with the susceptibility of cancer, and further functional research should be performed to explain the inconsistent results in different ethnicities and cancer types.