Genetic contribution between APE1 variants in polycystic ovarian syndrome

IntroductionPolycystic Ovarian Syndrome (PCOS) has been identified as a gynecological, hormonal, and metabolic condition in women of reproductive age. Genetic studies can contribute to understand the pathogenesis of PCOS; which can be beneficial in early diagnosis and long-term management of the disease. Apurinic/apyrimidinic endonuclease 1 (APE1) has been related in the literature to polycystic ovarian syndrome.AimThe purpose of this study was to investigate the effects of ?656 T > G and 1349 T > G single nucleotide polymorphisms (SNPs) in the APE1 gene in Saudi women with PCOS.MethodsThis study includes 100 PCOS women and 100 healthy controls were genotyped for ?656 T > G and 1349 T > G SNPs using PCR-RFLP method. Serum sample was used for FBG and lipid profile tests. The obtained biochemical and genotypes data were entered into Excel and utilized for statistical analysis.ResultsClinical data presented in Table 1 was used to calculate the t-tests between PCOS and control subjects and results indicate age, weight, BMI, TG, LDLC and PCOS family history was associated (p < 0.0001). Genotype and allele frequencies showed the negative association in ?656 T > G SNP (GG vs TT: OR-1.15 (0.61–2.17); p = 0.65 and GG + TG vs TT: OR-1.17 (0.67–2.04); p = 0.57) and positive association in 1349 T > G SNP (GG vs TT: OR-3.52 (1.48–8.36); p = 0.003 and GG + TG vs TT: OR-2.84 (1.27–6.31); p = 0.008) in APE1 gene. Anova analysis was not associated with any one of the involved parameters (p > 0.05).ConclusionThis study found that the 1349 T > G SNP was related with PCOS in Saudi women. However, the ?656SNP had no favorable effect on the APE1 gene.     

Independent case-control study in KCNJ11 gene polymorphism with Type 2 diabetes Mellitus

BackgroundType 2 Diabetes Mellitus (T2DM) is the most common form of diabetes in the aging population. This chronic metabolic disorder has discovered many candidate genes, and KCNJ11 was one of the genes associated with insulin secretion pathways mediated by potassium channels. There have been limited studies on the rs5210 polymorphism in T2DM patients, and none of them have been conducted in Saudi Arabia.AimThe aim of this study is to investigate at genotyping levels of rs5210 polymorphism in the KCNJ11 gene in older population with T2DM in the Saudi Population.MethodsBased on the sample size design, this case-control study included 102 T2DM cases and 102 controls. Using the PCR-RFLP assay, 204 patients extracted DNA was genotyped for the rs5210 polymorphism. SPSS software was used for statistical analysis, including t-tests, HWE, genotyping, and multiple logistic regression analysis.ResultsThe t-tests performed on T2DM cases and controls revealed a significant association in age, weight, BMI, FBG, Hb1Ac, SBP, DBP, HDLC, TC, and TG parameters (p < 0.05). HWE analysis found to be in consistent with rs5210 polymorphism. Allelic association was found in the rs5210 polymorphism (OR-1.64 [95 %CI: 1.08–2.49]; p = 0.01); however, no association (p > 0.05) was observed in the multivariate logistic regression assessment performed in this study.ConclusionThese results indicate that the rs5210 polymorphism was primarily associated with allele frequencies, which could be attributable to the small sample size. Large sample size studies will be required to determine whether KCNJ11 gene polymorphisms may be required as a risk marker for T2DM in the Saudi population.     

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 of angiotensin converting enzyme gene I/D polymorphism of vitiligo in Korean population

Vitiligo (leukoderma) is an acquired idiopathic hypomelanotic disorder characterized by the circumscribed depigmented patches. Vitiligo is a polygenic disease. The exact pathogenesis is not yet known. The angiotensin converting enzyme (ACE) gene was selected as a candidate gene as ACE plays an important role in the physiology of the vasculature, blood pressure and inflammation, and its relationship with various diseases, including autoimmune diseases, has been widely investigated. The I/D polymorphism of ACE gene in vitiligo patients has not been reported. In this study, we investigated ACE gene polymorphism in 120 vitiligo patients and in 429 healthy volunteers in Korea. The ACE gene genotype distribution (P = 0.032) and allele frequency (P = 0.012) were significantly different between vitiligo patients and healthy controls. This study suggests that the ACE gene polymorphism has a strong association with the development of vitiligo in Korean patients.     

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.     

Association between the lipoprotein lipase rs1534649 gene polymorphism in intron one with Body Mass Index and High Density Lipoprotein-Cholesterol

Lipoprotein lipase (LPL) is an enzyme involved in lipid metabolism and distribution of fatty acids hence its role in the initiation and development of dyslipidemia and adiposity. Single nucleotide polymorphisms (SNPs) across the LPL gene have been associated with dyslipidemia, however, the association with obesity has been limited towards specific populations. This study examined the association between LPL gene polymorphisms with plasma lipid levels and body mass index (BMI) in the Kuwaiti population. We examined a total of 486 adults (303 and 183 females and males respectively) with plasma lipid levels and BMI. DNA samples were genotyped for two LPL gene polymorphisms (rs1534649 and rs28645722) using TaqMan allelic discrimination. The relationship between the genotypes with both plasma lipid levels and BMI were assessed using linear regression using “SNPassoc” package from R statistical software. Using an additive genetic model, linear regression analysis showed the T-allele of rs1534649 to be associated with increased BMI in a dose-dependent trend β = 2.13 (95% CI 1.33–2.94); p = 1.7 × 10^?7. In addition, a borderline significance was observed between the T-allele and low levels of high density lipoprotein-cholesterol β = ?0.04 (95% CI ?0.08, ?0.006); p = 0.02. There were no associations between rs28645722 and plasma lipid levels (p > 0.05). However, a trend was observed between the A-allele and increased BMI β = 1.75 (95% CI 0.14–3.35); p = 0.03. Our study shows intron one polymorphism rs1534649 to increase the risk of obesity and dyslipidemia. Our findings warrant further investigation of the mechanism of LPL on the development of obesity along with the role of intron one and its impact on LPL gene activity.     

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.     

Protective and pathogenic role of collagen subtypes genes COL4A3 and COL4A4 polymorphisms in the onset of keratoconus in South-Asian Pakistani cohort

Collagen sub-types have an important role in corneal structure and are reported to be an important genetic predictor for keratoconus (KC) development, therefore we assessed the association of collagen subtypes by screening non-synonymous polymorphisms of COL4A3 and COL4A4 in South-Asian (Pakistani) patients.MethodsA total of 257 KC sporadic cases, gender and ethnicity matched 253 control individuals were screened for three non-synonymous single nucleotide polymorphisms (SNPs) rs55703767and rs10178458 in COL4A3 and rs2229814 and one synonymous SNP rs2228555 in COL4A4. The genotyping was done by Competitive Allele specific polymerase chain reaction (PCR) and the data were analyzed statistically.ResultsAmong the studied SNPs, the COL4A3 rs55703767 GT genotype (dominant model (DM): odds ratio (OR) = 0.243, (95 %CI) = 0.16–0.36, p=>0.0001), and allele-G (OR = 0.35, 95 %CI = 0.26–0.48, p < 0.000)), showed protective association against KC development. While COL4A3 rs10178458 CT genotype (DM: OR = 2.11(95 %CI = 1.16–3.85), COL4A4 rs2229814 TT genotype (RM: OR = 147.778(95 %CI = 20.401–1070.439), (p > 0.05) and allele-T (OR = 2.351(95 %CI = 1.826–3.028), (p > 0.05); COL4A4 rs2228555 AG genotype (DM: OR = 2.370(95 %CI = 1.594–3.524) (<0.0001) and GG genotype (RM: OR = 2.347(95 %CI = 1.587–3.472), (p < 0.0001); and allele-G (OR = 2.024(95 %CI = 1.577–2.597), (p > 0.0001) were observed to be disease associated.ConclusionCOL4A3 rs10178458 and COL4A4 SNPs rs2229814 and rs2228555 were found to be pathogenic for KC, whereas COL4A3 rs55703767 was found to play a protective role against KC development in South-Asian (Pakistani) Cohort.     

Contribution of genetic variant identified in HHEX gene in the overweight Saudi patients confirmed with type 2 diabetes mellitus

BackgroundThe rs7932837 polymorphism in the Hematopoietically expressed homeobox (HHEX) gene was discovered through genome-wide association studies and is a promising candidate for type 2 diabetes mellitus (T2DM), which is one of the risk factors for obesity and other complications. T2DM has been identified as a heterogeneous and multifactorial disease characterized by insulin resistance and secretion.AimThe aim of this study was to investigate the rs7932837 polymorphism in the HHEX gene in overweight patients diagnosed with T2DM in the Saudi Population.MethodsIn this case-control study, one hundred T2DM cases and 100 controls were selected based on inclusion and exclusion criteria. Genotyping was performed with polymerase chair reaction-restriction fragment length polymorphism analysis and statistical analysis was performed between T2DM cases and controls for clinical characteristics, genotype and allele frequencies and multiple logistic regression analysis.ResultsIn this study, T2DM cases were compared with healthy control subjects. Clinical characteristic analysis revealed the statistical analysis between age, weight, BMI, FBG, HDL-c, TC, TG and family history (p < 0.05). HWE analysis was in the accordance (p < 0.05). The rs7932837 polymorphism in the recessive model showed the positive association (AA + AG vs AA: 2.22 [1.25–3.96] & p = 0.006) and none of the genotypes or alleles were in the statistical association. Multiple logistic regression analysis revealed positive association with age, BMI and FBG (p < 0.05).ConclusionThis study concludes as rs7932837 polymorphism in the HHEX gene showed positive association with recessive model and future studies recommend to carry out with large number of sample size with additional polymorphisms in HHEX gene.     

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.     

Pharmacogenetics of Efficacy and Safety of HCV Treatment in HCV-HIV Coinfected Patients: Significant Associations with IL28B and SOCS3 Gene Variants

Background and Aims

This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients.

Methods

The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student''s T test, Mann-Whitney U test and logistic regression were used for statistic analyses.

Results

As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2–5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09–0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008–0.57, p = 0.01) remained significant.

Conclusions

In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism.     

Angiotensin-converting enzyme I/D polymorphism and the risk of thoracic aortic dissection in Chinese Han population

Thoracic aortic dissection (TAD) is a catastrophic cardiovascular disease and is thought to have a genetic basis. Various studies have indicated that renin-angiotensin system plays an important role in the pathogenesis of aortic disease. To determine the association of the I/D polymorphism of ACE gene with the risk of TAD in a Chinese Han population, a hospital-based case–control study was designed consisting of 161 subjects with TAD and 256 control subjects. The genotype frequency of the ACE I/D polymorphism was determined by using a polymerase chain reaction assay. The overall distribution of ACE I/D genotypes was significantly different between the two groups. Compared with the controls, the frequency of DD genotypes and the D allele of ACE gene were significantly increased in TAD patients. Multivariate logistic regression adjusting for conventional vascular risk factors confirmed the association between the ACE I/D polymorphism and the susceptibility to TAD (OR 2.14, 95 % CI 1.38–3.32, P = 0.001). Our data demonstrated that the ACE I/D polymorphism appeared to be an important risk factor in the development of TAD. However, further validation in large population-based studies is needed to confirm the finding.     

A study on the immunological vitality of an inflammatory biomarker explored with rs5743708 polymorphism in TLR2 gene among Saudi women confirmed with polycystic ovarian syndrome

IntroductionPolycystic ovary syndrome (PCOS) is an ovarian health condition as well as a long-term endocrine dysfunction that affects reproductive-aged women. Toll-like receptor 2 (TLR2) gene was linked to PCOS and chronic inflammation, and the prevalence of obesity was rising in Saudi women. Previous studies on rs5743708 polymorphism were documented in the obesity as well as in PCOS women.AimIn this study, we investigated the molecular role of rs5743708 polymorphism in TLR2 gene among Saudi women diagnosed with PCOS using the Rotterdam criteria.MethodsBlood samples were collected from 220 Saudi women in this hospital-based case-control study; 110 were PCOS women and remaining 110 were non-PCOS (control women). Biochemical analysis was performed on serum samples, and molecular analysis was performed on EDTA blood. Genotyping for rs5743708 polymorphism was performed with polymerase chain reaction-restriction fragment length polymorphism analysis.ResultsIn both groups, clinical data was calculated using t-test, which revealed both positive (p < 0.05) and negative (p > 0.05) associations. HWE analysis supported the rs5743708 polymorphism (p < 0.05). In the rs5743708 polymorphism, none of the genotypes, genetic models, or allele frequencies were found to be associated with PCOS and non-PCOS women. However, both ANOVA and regression analyses revealed a positive relationship in PCOS with weight and BMI (p < 0.0001).ConclusionThe rs5743708 polymorphism was not associated to PCOS in Saudi women. One of the predictions could be that 42.7% of PCOS and 73.6% of non-PCOS women were obese, and the rs5743708 polymorphism has been linked to both obesity and PCOS in the previous studies. This study suggests screening for additional polymorphisms with a large sample size.     

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the −786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects.A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and −786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR.There was significant linkage disequilibrium between the three NOS3 polymorphisms (p < 0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not −786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24–15.41; p = 0.021, dominant model OR: 1.66, 95%CI: 1.14–2.42); p = 0.007, and recessive model OR: 3.85, 95%CI: 1.10–13.47; p = 0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR = 12.05, p = 0.010) was a risk factor of MI after controlling for classical risk factors.These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.     

Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa

Background

Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa.

Methods and Findings

A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52–2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23–1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04–1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30–2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas.

Conclusion

This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.     

Screening of mitochondrial mutations and insertion–deletion polymorphism in gestational diabetes mellitus in the Asian Indian population

In this study we scrutinized the association between the A8344G/A3243G mutations and a 9-bp deletion polymorphism with gestational diabetes mellitus (GDM) in an Asian Indian population. The A3243G mutation in the mitochondrial tRNA^Leu(UUR) causes mitochondrial encephalopathy myopathy, lactic acidosis, and stroke-like episodes (MELAS), while the A8344G mutation in tRNA^Lys causes myoclonus epilepsy with ragged red fibers (MERRF). We screened 140 pregnant women diagnosed with GDM and 140 non-GDM participants for these mutations by PCR-RFLP analysis. Both A3243G and A8344G were associated with GDM (A3243: OR-3.667, 95% CI = 1.001–13.43, p = 0.03; A8344G: OR-11.00, 95% CI = 0.6026–200.8, p = 0.04). Mitochondrial DNA mutations contribute to the development of GDM. Our results conclude that mitochondrial mutations are associated with the GDM women in our population. Thus it is important to screen other mitochondrial mutations in the GDM women.     

Relationships between digit ratio (2D:4D), ACE gene polymorphism, and physical performance in the Korean population

The aim of this study is to assess the possible contribution of the ratio of the length of second-to-fourth digits (2D:4D) and angiotensin-converting enzyme (ACE) gene variants to differences in elite athletic performance. We have therefore examined a population-based association study in 151 Korean elite athletes and 183 controls with the digit ratio (2D:4D) and I/D polymorphism of ACE gene. Genotype distribution of the ACE gene showed no significant deviation from Hardy-Weinberg equilibrium in both groups of elite athletes and controls. No statistically significant difference in the distribution of the ACE genotype frequency was observed between the elite athletes and control groups. In contrast, the digit ratio (2D:4D) appeared to be statistically significant difference between the elite athletes and control groups (p<0.001), although there was no genotype effect of the ACE gene on the digit ratio (2D:4D) in this survey. Thus, our data are consistent with hypothesis that digit ratios, as markers for prenatal testosterone action may provide a significant effect on elite athlete status, although larger sample sizes functional studies are necessary to further substantiate these findings.     

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.     

Angiotensin-converting enzyme gene polymorphism is associated with type 2 diabetes: a meta-analysis

The association of angiotensin-converting enzyme gene polymorphism with type 2 diabetes was investigated in many studies with conflicting results. To clarify this conflict, we performed a meta-analysis on recent previous reports on ACE gene polymorphism and its correlation to type 2 diabetes. A total of 15,166 subjects from 24 studies were included in this meta-analysis. Summary odds ratios (ORs) were estimated. Potential sources of heterogeneity and bias were explored. The D variant was associated with a 14% increased risk of T2D relative to the I variant (OR 1.14; 95% CI: 1.04–1.24). In subgroup analysis, Caucasian and East Asians showed significant association. No association was found in the Turkish groups. No publication bias was observed in this meta-analysis by using the Egger method (τ = 1.63, P = 0.12), as well as the Begg’s test (z = 1.66, P = 0.10). Cumulative meta-analysis for the allelic contrast showed a trend of association as information accumulated. These data suggested that the variant of ACE I/D had a moderate positive association with type 2 diabetes.