Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease in Indian population and meta-analysis

Rheumatic heart disease (RHD) is one of the most severe consequences of rheumatic fever. It has been suggested that angiotensin I-converting enzyme (ACE) may be involved in the increased valvular fibrosis and calcification in the pathogenesis of RHD. We conducted a case–control study to look for association of ACE I/D polymorphism with RHD in Indian population. The study incorporated 300 patients (170 males and 130 females) with RHD, and 200 controls (118 males and 82 females). We also subgrouped RHD patients into mitral valve lesion (MVL) and combined valve lesion (CVL). ACE I/D polymorphism was identified using polymerase chain reaction method. We also performed a meta-analysis of three published studies and the present study (636 RHD cases and 533 controls) to evaluate the association between the ACE I/D polymorphisms and RHD risk. A significant difference in ACE ID and DD genotypes distribution between RHD cases (OR = 1.62, 95 % CI = 1.11–2.36 and OR = 2.08, 95 % CI = 1.02–4.15, respectively) and corresponding controls was observed. On comparing the ACE genotypes of MVL and CVL subgroups with controls, ID and DD genotypes were also significantly associated with CVL (FDR Pcorr = 0.009, OR = 2.19 and FDR Pcorr = 0.014, OR = 3.29, respectively). Meta-analysis also suggested association of the ACE D allele (FDR Pcorr = 0.036, OR—1.22, 95 % CI 1.02–1.45) with RHD. In conclusion, ACE ID and DD genotypes are associated with an increased risk of RHD, particularly CVL. This suggests that the ACE I/D gene polymorphism may play an important role in the pathogenesis of RHD.     

Angiotensin converting enzyme gene polymorphism studies: A case-control study

Mild gestational hyperglycemia (MGH) is a very common complication of pregnancy that is characterized by intolerance to glucose. The association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to MGH has been previously reported. In this study, we evaluated the association between ACE polymorphism and the risk of MGH in a Saudi population. We conducted a case-control study in a population of 100 MGH patients and 100 control subjects. ACE gene polymorphism was analyzed by the novel approach of tetraprimer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequency of ACE polymorphism was not associated with either alleles or genotypes in MGH patients. Glucose concentration was found to be significantly associated with the MGH group. Our study suggests that ACE genotypes were not associated with ACE polymorphism in a Saudi population.     

Association between ACE I/D polymorphism and pulmonary tuberculosis in Chinese population

Tuberculosis (TB) remains a global public health problem worldwide. The objective of the current study is to investigate the possible association of ACE I/D polymorphism with pulmonary TB (PTB) for Chinese in Sichuan province. Three hundred eighty-six PTB patients and 398 healthy controls were genotyped to analyze the I/D polymorphism using PCR method. The results showed that the I/D polymorphism was not associated with susceptibility to PTB for Chinese (D vs. I: OR 1.03, 95 % CI 0.84–1.26, and P = 0.77; DD vs. II+DI: OR 1.09, 95 % CI 0.73–1.63, and P = 0.68; DD+DI vs. II: OR 1.00, 95 % CI 0.74–1.33, and P = 0.98). The I/D polymorphism in the ACE gene may not a risk factor for PTB in Chinese.     

Association of the ACE-II genotype with the risk of nephrotic syndrome in Pakistani children

Nephrotic syndrome is a common pediatric glomerular disease associated with heavy proteinuria. Since, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is a putative genetic risk factor for NS, in this study, ACE (I/D) polymorphism was analyzed in 268 NS and 223 control samples by a PCR-based method. The genotypic and allelic frequencies were determined and the association between ACE I/D polymorphism and NS was evaluated. The frequency distribution of the II, ID and DD genotypes was 82 (30.6%), 128 (47.8%) and 58 (21.6%) in the NS patients and 9 (4.0%), 171 (76.7%) and 43 (19.3%) in the control samples respectively. In the Pakistani pediatric NS population, the II genotypic and allelic frequencies were found to be significantly associated with the disease (OR = 6.755; C.I = 3-14.9). No significant association was found between this polymorphism and the response to standard steroid therapy. Thus, in contrast to reports from other parts of the world, the II genotype was found to be significantly associated with NS in the Indian and Malay populations and in the Pakistani population described here. To our knowledge, this is the first report from Pakistan describing the association of the ACE I/D polymorphism with pediatric NS. On the basis of these results, it is suggested that analysis of the ACE (I/D) polymorphism should be performed for the early diagnosis in the high risk NS patients in South Asia.     

The ACE polymorphism is associated with BMI in patients with metabolic syndrome

The angiotensin-converting enzyme (ACE) polymorphism is well known to be associated with cardiovascular diseases. Until now, however, evidence for the role of ACE polymorphism in susceptibility to metabolic syndrome (MS) has not been well studied. Thus, we investigated an association between ACE polymorphisms and Korean patients with MS. DNA samples from 214 MS patients and 193 age-matched non-MS subjects were amplified using the polymerase chain reaction for detection of the ACE insertion/deletion (I/D) and BstUI polymorphisms. Anthropometric and physiological parameters including body mass index (BMI), waist circumference, blood pressure, glucose, triglycerides, total cholesterol and HDL cholesterol were measured. The genotype frequencies of the ACE I/D and BstUI polymorphisms were not significantly different between the non-MS and the MS group. The BB genotype distribution of the BstUI polymorphism in the female subgroup, however, was associated with an increased risk of MS (P = 0.008). When the data were stratified by BMI values, the high BMI groups showed significant differences between the non-MS and the MS groups, compared to the low BMI group, in all genotype frequencies of the ACE I/D and BstUI polymorphisms. The trend remained even when the genotypes of the two polymorphisms were combined. Although no consistent results were obtained on the association between the ACE polymorphism and MS in the populations studied, the ACE polymorphism, at least in Koreans, may be a genetic determinant of BMI in MS patients. Therefore, further studies are required on the association between the ACE polymorphism and MS patients in other racial or ethnic groups.     

Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and rheumatoid arthritis

We sought to determine the frequency of I/D polymorphism genotypes of angiotensin converting enzyme gene in Turkish patients with rheumatoid arthritis. Genomic DNA obtained from 256 individuals (110 patients with rheumatoid arthritis and 146 healthy controls) was used in the study. ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. There was a statistically significant difference between the groups with respect to genotype distribution (p = 0.001). A significant difference was found in frequencies of ACE I/D alleles between patients and controls, with RA patients having a higher representation of D and lower representation of I alleles compared to controls (p < 0.001). As a result of our study, angiotensin converting enzyme gene I/D polymorphism DD genotype could be a genetic marker in rheumatoid arthritis in the Turkish study population.     

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.     

Molecular analysis of genetic variation in angiotensin I-converting enzyme identifies no association with sporting ability: First report from Indian population

INTRODUCTION:

A polymorphism in the angiotensin-converting enzyme (ACE) gene was the first performance enhancing polymorphisms (PEPs) to be identified and correlated with athletic abilities. This polymorphism (rs. 5186) is the absence (deletion; D allele), rather than the presence (insertion, I allele) of 287bp Alu repeat element in intron 16. However, the association of ACE I/D polymorphism in sports abilities have been contradicted and debated. No study has evaluated the ACE gene polymorphism in Indian athletes so far. Hence, the genotype distribution and allelic frequency of ACE gene in selected Indian athletic and non-athletic population was studied.

MATERIALS AND METHODS:

A total of 147 athletes and 131 controls were genotyped for the ACE gene polymorphism using PCR.

RESULTS:

No significant association was observed between the allelic frequencies of ACE gene in controls and athletes on a whole, as well as after sub-categorizing the athletes based on the type of sport they played (P > 0.1). However, a higher representation of I allele was observed in the athletes.

CONCLUSION:

ACE genotyping studies need to focus on truly elite athletes of a single sporting discipline, to be able to find an association. The ACE I/D polymorphism may not be considered a marker for human performance, but can be further studied in combination with other potent performance enhancing polymorphisms.     

Genetic Predisposition for Development of Nephropathy in Type 2 Diabetes Mellitus

The aim of the study was to explore the association of the angiotensin-converting enzyme (ACE) gene I/D polymorphism and the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with development of diabetic nephropathy in type 2 diabetes mellitus. Three groups were recruited during 2007–2011: 232 normal controls, 185 type 2 diabetics without nephropathy, and 407 type 2 diabetics with nephropathy. The ACE I/D and MTHFR C677T polymorphisms were examined using PCR and PCR-RFLP methods. We found no significant association of the ACE I/D polymorphism with diabetic nephropathy in genotype, allele, dominant, and recessive models. We observed a significant association of MTHFR C677T with development of diabetic nephropathy in type 2 diabetics. The MTHFR C677T polymorphism plays a significant role in predisposition of renal insufficiency in diabetic patients.     

Association of AGTR1 (A1166C) and ACE (I/D) Polymorphisms with Breast Cancer Risk in North Indian Population

Renin angiotensin system (RAS) comprising Angiotensin converting enzyme (ACE), Angiotensin II (Ang II) and its receptor Angiotensin II receptor type I (AGTR1), plays a critical role in several diseases including cancer. A single nucleotide polymorphism (SNP) A1166C located in 3′ untranslated region (UTR) of AGTR1 and an insertion/deletion (I/D) polymorphism present in intron 16 of ACE gene have been associated with many diseases, but their association with Breast cancer (BCa) is still debatable. Here, we for the first time investigated the association of these polymorphisms in a North Indian BCa cohort including 161 patients and 152 healthy women. The polymorphisms were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) respectively. The association between these polymorphisms and BCa risk was estimated by calculating Odds Ratio (OR) and chi-square (χ²) test. The DD genotype/D allele of ACE (I/D) polymorphism and “AC and CC” genotype/C allele of AGTR1 (A1166C) polymorphism were associated with higher risk of BCa when evaluated independently. Furthermore, interaction analysis of “AC and CC” and DD genotype and combination of “C and D” alleles of both polymorphisms revealed significantly greater BCa risk than that observed independently. Conclusively, women harboring “AC or CC” genotype/C allele for AGTR1 (A1166C) polymorphism and DD genotype/D allele for ACE (I/D) polymorphisms have a predisposition to develop more aggressive disease with advanced staging and larger tumor size. Our study indicates importance of genetic screening based on these polymorphisms for women, who may have higher risk of BCa.     

Effects of Common Polymorphisms in the MTHFR and <Emphasis Type="Italic">ACE</Emphasis> Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis

Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR?=?1.43, 95 % CI 1.12–1.83, P?=?0.004) and MTHFR 677 C>T mutation (OR?=?1.43, 95 % CI 1.08–1.90, P?=?0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P?<?0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.     

Deleterious effect of angiotensin-converting enzyme gene polymorphism in vitiligo patients

Vitiligo is a rare skin condition caused by an immune reaction. Vitiligo can occur anywhere on the body. This proposed explanation of vitiligo makes it clear that vitiligo is not linked to any other autoimmune diseases. The polymorphisms of some genes present in the immune system play a major function in susceptibility of vitiligo. Meta-analysis studies have shown that the Angiotensin converting enzyme (ACE) gene insertion and deletion polymorphism is closely associated with vitiligo in many ethnicities. The connection between ACE gene and vitiligo is connected through the auto immune diseases and there are no genetic polymorphism studies have been carried out with ACE gene with vitiligo in the Saudi population. Previous studies show that vitiligo patients are more likely to also have an autoimmune disorder. The current study aims to investigate the I/D polymorphism in the ACE gene with diagnosed patients with vitiligo subjects. This is a case-control study carried out in the Saudi population with 100 vitiligo cases and 100 healthy controls. Genotyping was performed through polymerase chain reaction followed by 3% agarose gel electrophoresis. Genotype and allele frequencies were carried out with genetic mode of inheritances. Statistical analysis was performed considering p < 0.05 as significant association. There was a substantial difference in allele frequency distribution between vitiligo patients and healthy controls (OR-1.70 (95%CI: 1.14–2.53); p = 0.008). Additionally, DD genotype (OR-4.71 (95%CI: 1.42–15.61); p = 0.008) and recessive model (OR-2.66 (95%CI: 1.41–5.02); p = 0.002) was strongly associated. Both dominant and co-dominant showed the negative association (p > 0.05) when compared between the vitiligo cases and controls. The correlation between age and genotyping was performed with Anova analysis and current study results confirmed the substantial link between 11 and 20 years (p = 0.01) and 31–40 years (p = 0.04) with the defined age groups. In conclusion, in Saudi populations, the ACE gene I/D polymorphism was identified as being correlated with vitiligo. This is the first study in Saudi Arabia to report the risk factors of vitiligo with the ACE gene polymorphism.     

Influence of Alpha-2-Macroglobulin 5 bp I/D and Ile1000Val Polymorphisms on the Susceptibility of Alzheimer’s disease: A Systematic Review and Meta-analysis of 52 Studies

Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and Ile1000Val (rs669) polymorphisms with Alzheimer’s disease (AD) risk, but the results remain inconclusive. To investigate whether these two polymorphisms facilitate the susceptibility to AD, we conducted a comprehensive systematic review and meta-analysis. Databases of PubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to get the genetic association studies. All statistical analyses were conducted with Review Manager 5.2 and STATA11.0. Fifty-two articles were included in the final meta-analysis. We performed meta-analysis of 39 studies involving 8,267 cases and 7,932 controls for the 5 bp I/D polymorphism and 27 studies involving 6,585 cases and 6,637 controls for the Ile/Val polymorphism. Overall results did not show significant association between these two polymorphisms and AD risk in dominant, recessive, and multiplicative genetic models. On the stratification analyses by ethnicity and APOE ε4 status with genotypes of polymorphism sites, similar negative associations were found. The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites. However, due to the heterogeneity in the meta-analysis, the results should be interpreted with caution.     

Association between the −1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being ?1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between ?1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for ?1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the ?1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169–4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879–4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787–1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737–1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the ?1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.     

Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy: evidence from a meta-analysis

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.     

Effects of Interaction between Angiotensin I‐Converting Enzyme Polymorphisms and Lifestyle on Adiposity in Adolescent Greeks

Genetic variation in the human angiotensin I‐converting enzyme (ACE) gene has been associated with many heritable traits, including obesity. Herein, we report the results of a study of obesity‐related phenotypes and lifestyle in 1016 teen‐aged Greeks. We show that there is a strong association (p = 0.001) between subcutaneous fat and the ACE insertion/deletion (I/D) polymorphism in females, possession of genotypes containing the D allele being associated with increased fat thickness. This association is strongest in females who participate in no extra exercise and accounts for 6.5% of the phenotypic variance in fat thickness by ANOVA. The association is additive, with the mean phenotypic values in heterozygotes intermediate between the means of the two homozygotes, and the association acts at both extremes of the fat thickness distribution in a classical polygenic manner. Other ACE polymorphisms (rs4424958, rs4311) that define major haplotypes in European populations fail to provide stronger associations with the subcutaneous fat phenotype. Because ACE I/D is the polymorphism most strongly associated with circulating ACE levels in European populations, we propose that the functional allelic differences that influence circulating ACE levels also mediate the associations with the obesity‐related phenotypes studied here.     

Association of angiotensin-converting enzyme and endothelial Nitric Oxide synthase gene polymorphisms with vascular disease in ESRD patients in a Chinese population

Background The effect of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and endothelial Nitric Oxide synthase (eNOS) gene G894 → T on vascular disease in end-stage renal disease (ESRD) patients was rarely studied previously. We investigated such effect in a Chinese population. Methods A total of 153 ESRD patients with vascular disease (88 men and 65 women; mean age ± SD: 54.0 ± 13.2) were recruited. Polymerase chain reaction was used to classify the ACE genotypes as II, ID and DD and the eNOS genotypes as GG, GT, and TT. Analyses were performed in ESRD patients with vascular disease (n = 153) and the age-matched controls (n = 148). Results The frequencies of ACE DD and eNOS TT genotypes and ACE D and eNOS T alleles in ESRD patients with vascular disease were significantly higher than those in the controls (P < 0.05). There was a significant interaction between ACE I/D alleles and eNOS G894 → T polymorphism: adjusted odds ratio 2.128 (95%CI 1.022–4.434, P = 0.017). Conclusions These results indicated that the etiology of vascular disease in ESRD patients is associated with ACE and eNOS (G894 → T) gene polymorphisms. Our data also suggest that an interaction effect may exist between ACE (I/D) and eNOS (G894 → T) polymorphism in increasing the risk of vascular complications in ESRD patients     

Novel SNPs and INDEL polymorphisms in the 3′UTR of DGAT1 gene: in silico analyses and a possible association

Diacylglycerol–O–acyltransferase (DGAT1) gene encodes the rate-limiting enzyme of triglyceride synthesis. A polymorphism in this gene, DGAT1 K232A, has been associated with milk production and composition in taurine breeds. However, this polymorphism is not a good tool for ascertaining the effects of this QTL in Bos indicus (Zebu), since the frequency of the DGAT1 232A allele is too low in these breeds. We sequenced the 3′-untranslated region of DGAT1 gene in a sample of bulls of the breeds Guzerá (Bos indicus) and Holstein (Bos taurus) and, using in silico analysis, we searched for genetic variation, evolutionary conservation, regulatory elements, and possible substitution effects. Six single nucleotide (SNPs) and one insertion-deletion (INDEL) polymorphisms were found in the Guzerá bulls. Additionally, we developed a preliminary association study, using this INDEL polymorphism as a genetic marker. A significant association was detected (P ≤ 0.05) between the INDEL (DGAT1 3′UTR INDEL) and the breeding values (BV) for protein, fat, and milk yields over a 305-day lactation period. The DGAT1 3′ UTR INDEL genotype I/I (I, for insertion) was associated with lower BVs (?38.77 kg for milk, ?1.86 kg for fat, and ?1.48 kg for protein yields), when compared to the genotype I/D (D, for deletion). I/D genotype was lower D/D genotype (?34.98 kg milk, ?1.73 kg fat, and ?1.09 kg protein yields). This study reports the first polymorphism of DGAT1 3′UTR in the Guzerá breed, as well as its association with BV for milk protein, fat, and milk yields.     

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes to Ischemic Stroke Risk: A Meta-Analysis of 50 Case-Control Studies

Background

Many studies have investigated the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of ischemic stroke. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a large meta-analysis of studies relating the ACE I/D polymorphism to the risk of ischemic stroke.

Methods

Relevant studies were identified by searching PubMed and Embase through February 2012 and by reviewing the references of retrieved articles. We included studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between this polymorphism and ischemic stroke risk.

Results

Fifty independent publications, with 10 070 stroke cases and 22 103 controls, were included. The results indicated that the DD homozygote carriers had a 37% higher risk of ischemic stroke when compared with the homozygotes II and heterozygote ID [odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.22–1.53]. Subgroup analyses indicated that this higher risk was more pronounced among Asians, hospital-based studies, and small vessel disease (SVD). Potential publication bias may exist, but correction for this bias using a formal statistical method did not materially alter the combined risk estimate.

Conclusion

The results of our meta-analysis indicate that the D allele of ACE I/D polymorphism is a low-penetrance susceptibility marker of ischemic stroke.     

The association between estrogen receptor alpha polymorphisms and the risk of prostate cancer in Slovak population

The aim of our study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, PvuII and XbaI, on the development of prostate cancer within Slovak population, as well as their correlation with selected clinical characteristics. The study was performed using 311 prostate cancer patients and 256 healthy male controls. Both polymorphisms were significantly associated with higher risk of prostate cancer development. At the same time, the CC genotype of PvuII polymorphism (OR = 1.98; 95 % CI 0.94–4.21; p = 0.05) and the AG genotype of XbaI polymorphism (OR = 1.74; 95 % CI 1.0–3.02; p = 0.04) significantly contributed to the development of low-grade carcinoma, while the AG and GG genotypes of the XbaI polymorphism contributed mainly to the development of high-grade prostate cancer (OR = 1.83; 95 % CI 1.12–3.01; p = 0.01 and OR = 2.13; 95 % CI 1.06–4.19; p = 0.03, respectively). Similarly, the AG and GG genotypes of XbaI polymorphism showed significant association with prostate cancer in patients with serum PSA level ≥10 ng/ml. Both polymorphisms were found at the same time to be more frequent in patients diagnosed before the age of 60. We conclude on the basis of these results that PvuII and XbaI polymorphisms of estrogen receptor alpha might be associated with prostate cancer risk within Slovak population. Although this is a pilot study and, as such, more detailed investigations are needed to confirm the role of these polymorphisms in prostate cancer development and progression within said Slovak population, our results might still provide a valuable basis for further research with larger patient groups.