Rs1799983 Polymorphism Research Articles

Association of the single nucleotide polymorphism in chromosome 9p21 and chromosome 9q33 with coronary artery disease in Chinese population

BackgroundOur study aims to explore the association of rs7025486 single-nucleotide polymorphisms (SNP) in DAB2IP and rs1333049 on chromosome 9p21.3 with the coronary artery disease in Chinese population.MethodsAll patients came from the east China area and underwent coronary angiography. Rs7025486 and rs1333049 polymorphism were genotyped in 555 patients with CAD and in 480 healthy controls that underwent coronary angiography.ResultsIn Chinese population, the rs7025486 genotype in the case group was no significant different than the control group (P = 0.531).Meanwhile, the rs1333049 SNP has statistically significant (P = 0.006), which was the independent risk factors for CAD (OR1.252, P = 0.039), and consistent with the past studies conclusion.ConclusionGenotype of rs1333049 on chromosome 9p21, but not rs7025486 on chromosome 9q33, is an independent determinant of the incidence of CAD in Chinese population.

Rs3918242 variant genotype frequency and increased TIMP-2 and MMP-9 expression are positively correlated with cancer invasion in urinary bladder cancer.

To study the role of MMP9 and TIMP2 genotypes and expression in predisposition to bladder cancer and relation with metastasis. 100 urinary bladder cancer patients and 100 healthy controls were included in the study. rs3918242 and rs8179090 genotypes were determined with PCR-RFLP. Quantitative real-time polymerase chain reaction was employed to assessthe MMP-9 and TIMP-2 expression in tumors and adjacent healthy tissues. Variant genotype (TT) for rs3918242 polymorphism and rs8179090 variant genotype are not associated with bladder cancer risk. rs3918242 genotype was significantly associated with tumor invasion. In contrast with this, rs8179090 genotype has not shown a significant association with tumor invasion. Both SNPs did not show a significant association with metastatic status. MMP-9 was upregulated in tumors in comparison to cancer free tissues. Significant increase in the expression of MMP-9 was also observed in invasive tumors. TIMP-2 expression was significantly increased in tumors in comparison to cancer free tissues and in metastatic tumors in comparison to non-metastatic tumors. Tissues with rs3918242 variant genotype have shown increased MMP-9 expression. rs3918242 promoter polymorphism of MMP-9 is significantly associated with tumor invasion, however; there is no positive correlation between TIMP-2 rs8179090 promoter polymorphism variant frequency and invasion. MMP-9 and TIMP-2 genes are upregulated in cancerous tissues when compared to normal bladder tissues.

Designing and Validation of One-Step T-ARMS-PCR for Genotyping the eNOS rs1799983 SNP.

Background: The transversion of G to T (G894T) in human endothelial nitric oxide synthase (eNOS) gene has profound effects such as male infertility, recurrent miscarriage, multiple sclerosis and cardiovascular diseases. Objectives: Development of a new Multiplex Tetra-Primer Amplification Refractory Mutation System - Polymerase Chain Reaction (T-ARMS-PCR) for detection of rs1799983 (G894T) in the human eNOS was sought. Materials and Methods: A T-ARMS-PCR for rs1799983 polymorphism in a single-step PCR was carried out, and the results were confirmed by PCR-RFLP technique in 82 infertile men with varicocele. Results: The results showed that GG (varicocele infertile men), GT and TT genotypes appear to be 53.65%, 34.14%, and 12.19%, respectively. Full accordance between PCR-RFLP and T-ARMS-PCR methods for genotyping of rs1799983 polymorphism was found. Conclusions: This is the first work that describes a rapid, relatively cheap, high throughput detection of G894T polymorphism in eNOS that can be used in large scale clinical studies.

Associations of cholesteryl ester transfer protein (CETP) gene variants with predisposition to age-related macular degeneration

PurposeTo determine the frequency of the genotypes of single nucleotide polymorphisms (SNPs) in the gene encoding cholesteryl ester transfer protein (CETP) and their associations with age-related macular degeneration (AMD) in the Lithuanian population. Study designA total of 1264 subjects were examined: 251 patients with early AMD, 206 patients with exudative AMD, and 807 healthy controls. MethodsThe genotyping of CETP (rs5882, rs708272, rs3764261, rs1800775, rs2303790) was carried out using the RT-PCR. ResultsBinomial logistic regression analysis revealed that each copy of rs5882 allele A was associated with a 1.3-fold increased risk of exudative AMD (p=0.046). The G/A and A/A genotypes of the rs708272 polymorphism were associated with 1.5-fold and 1.7-fold increased risks of exudative AMD (p=0.049 and p=0.021, respectively). Combination of two genotypes (G/A+A/A) under the dominant model were associated with a 1.5-fold increased risk of exudative AMD (p=0.021).Analysis of rs708272 revealed that the G/A and A/A genotypes under the co-dominant model were associated with 1.5-fold and 1.7-fold increased risks of exudative AMD, respectively (OR=1.450, 95% CI=1.002–2.098; p=0.049 and OR=1.710, 95% CI=1.064–2.156; p=0.021, respectively). Both genotypes (G/A+A/A) under the dominant model were associated with the 1.5-fold increased risk of exudative AMD, as well (OR=1.514, 95% CI=1.064–2.156; p=0.021) and each additional copy A allele was associated with a 1.3-fold increased risk of exudative AMD (OR=1.316, 95% CI=1.051–1.646; p=0.016). The rs3764261 polymorphism was identified to be protective: the C/A genotype and the combination of two genotypes (C/A+A/A) were associated with 1.8-fold and 1.5-fold decreased risks of exudative AMD (p=0.001 and p=0.015, respectively). ConclusionOur study identified two polymorphisms with a higher risk of AMD development (rs5882 and rs708272) and a protective polymorphism for AMD (rs3764261).

The rs10757278 Polymorphism of the 9p21.3 Locus in Children with Arterial Ischemic Stroke: A Family-Based and Case-Control Study

The association of 9p21.3 locus single nucleotide polymorphisms with arterial ischemic stroke in adults was demonstrated in many studies, but there are no studies in pediatric arterial ischemic stroke patients. We investigated whether the 9p21.3 locus polymorphism, namely rs10757278, is associated with the arterial ischemic stroke risk in children. The study group consisted of 335 individuals: 80 children with arterial ischemic stroke, their biological parents (n = 122), and 133 children (age and sex matched) without any symptoms of arterial ischemic stroke as a control group. The rs10757278 polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). Two different study design models were used: family-based association test (transmission-disequilibrium test) and case-control model. There were no statistically significant differences in the distribution of genotypes and alleles of the rs10757278 polymorphism between groups of children with arterial ischemic stroke and controls. The frequency of both transmitted alleles in transmission-disequilibrium test analysis was identical (50%). The A allele carrier state (AA+AG genotype) was more frequent in arterial ischemic stroke children with hemiparesis than in patients without this symptom (94.5% versus 68.0%, P = .004). There is no evidence to consider the 9p21.3 locus polymorphism as a risk factor for childhood arterial ischemic stroke.

COX2 and NOS3 gene polymorphisms in women with gestational diabetes.

Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnancy. Low-grade inflammation plays an important role in the pathogenesis of this disorder. The present study aimed to examine the association between COX2 (rs6681231) and NOS3 (rs1799983 and rs2070744) gene polymorphisms and GDM. The study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28weeks of gestation. We observed an increased frequency of COX2 rs6681231 CC and GC genotype carriers among women with GDM (CC+GC versus GG, odds ratio=1.55, 95% confidence interval=1.01-2.36, p=0.043; C versus G, odds ratio=1.59, 95% confidence interval=1.10-2.30, p=0.013). There were no statistically significant differences in the distribution of NOS3 rs1799983 and rs2070744 between GDM and healthy women. Moreover, among women treated with insulin, we observed an increased frequency of COX2 rs6681231 CC and NOS3 rs1799983 TT genotype carriers. The results of the present study suggest that the CC genotype of the COX2 rs6681231 polymorphism is associated with an increased risk of GDM and the need for insulin therapy, whereas the TT genotype of the NOS3 rs1799983 polymorphism may be associated with the need for insulin therapy in women with GDM.

Logic Regression Analysis of Gene Polymorphisms and HDL Levels in a Nationally Representative Sample of Iranian Adolescents: The CASPIAN-III Study.

BackgroundTo investigate the associations of genetic polymorphism with high-density lipoprotein-cholesterol (HDL-C) levels in Iranian adolescents.MethodsThis multicentre study was conducted on 10 - 18 year-old students from 27 provinces in Iran. Logic regression approach was used to determine the main effects and interactions of polymorphisms related to HDL-C levels.ResultsThe rs708272 polymorphism was significantly related to HDL-C levels. Moreover, rs708272 increased HDL-C levels and had a protective effect on HDL-C. The interaction of rs2230808 and rs5880 polymorphisms as well as the interaction of rs320 and rs708272 polymorphisms were associated with lower HDL-C levels. Furthermore, the interaction of rs320 and rs1801177 polymorphisms was associated with lower HDL-C levels.ConclusionsWe found that not only single SNPs, but also interactions of several SNPs affect HDL-C levels. Given the high prevalence of low HDL-C in Middle Eastern populations, further genetic studies are required for detailed analysis.

Erratum to: Association Study between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population

In this study, we verify the association between the rs1333049 single nucleotide polymorphism (9p21.3) within CDKN2A-CDKN2B and coronary artery disease (CAD) in an Italian population. We replicated rs1333049_G allele association with a significantly reduced risk of CAD (OR = 0.816; 95% confidence interval [0.705-0.945]; p = 0.0065) in 711 CAD patients and 755 normal healthy individuals. This effect is maintained even stratifying patients by gender and by risk factors. A significant association was found with age of CAD onset. Interestingly, we found a protective trend of association between the rs1333049_G allele and peripheral artery disease, a progressive atherosclerotic condition in which plaque builds up in the arteries that carry blood to the head, organs, and limbs (OR = 0.724; 95% CI [0.520-1.007]; p = 0.054). No genotype-phenotype association was found with more severe CAD clinical parameters. If certain genetic factors predispose individuals to adverse outcomes, the knowledge of a patient's genotype may influence clinical management.

Collagen Type I Alpha 2 (COL1A2) Polymorphism Contributes to Intracranial Aneurysm Susceptibility: A Meta-Analysis.

BackgroundCOL1A2, which encodes collagen type I alpha2, has long been suggested to be a potential positional and functional candidate gene for intracranial aneurysm. We performed a meta-analysis to assess the association between COL1A2 rs42524 polymorphism and the risk of intracranial aneurysm.Material/MethodsWe conducted a systematic search for relevant literature from the following databases up to 22 July 2016: PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The strength of association between gene and disease was estimated using odds ratios (ORs) with 95% confidence intervals (CIs) under 5 genetic models.ResultsA total of 6 qualified studies were enrolled in this meta-analysis. Pooling results indicated a significant association between COL1A2 rs42524 polymorphism and intracranial aneurysm risk under 4 genetic models (C vs. G: OR=1.74, 95%CI=1.34–2.26; GC vs. GG: OR=1.81, 95%CI=1.37–2.41; CC+GC vs. GG: OR=1.74, 95%CI=1.28–2.36; CC vs. GC+GG: OR=1.76, 95%CI=1.02–3.04). This association was still robust when stratified by ethnicity, intracranial aneurysm type, or Hardy-Weinberg Equilibrium, which was stronger in Asian than in Caucasians. No publication bias was observed.ConclusionsThis meta-analysis suggests COL1A2 rs42524 is a significant risk factor for IA susceptibility, with an especially strong effect in Asian people. Further larger-scale epidemiological studies among different ethnicities are warranted to confirm our findings.

The placental vascular endothelial growth factor polymorphisms and preeclampsia/preeclampsia severity

ABSTRACTPreeclampsia (PE) is a serious pregnancy-specific condition, which originates from placenta and finishes after delivery. The present study has investigated the association between placental VEGF I/D (rs35569394), −1154G/A (rs1570360), and −634G/C(rs2010963) polymorphisms and maternal VEGF −2549 I/D (rs35569394) polymorphism with PE and PE severity.In this case-control study, the maternal blood of 217 women with PE and 210 normotensive pregnant women and the placenta of 84 PE women and 103 normotensive women were collected after delivery. Genotyping was done by PCR or PCR-RFLP methods.The maternal VEGF-2549I/D genotypes were not associated with PE or PE severity. The placental VEGF −2549 I/D genotypes were not associated with PE too; however; the placental VEGF-2549 DD genotype was statistically different between women with severe PE and mild PE or the controls. The placental VEGF −634GC and CC genotypes were significantly higher in PE women and associated with 2.6 and 2-fold higher risk of PE, respectively. The VEGF −634GC and CC genotypes were associated with PE severity. No association was found between placental VEGF −1154G/A polymorphism and PE or PE severity. The placental DGC haplotype of VEGF −2549 I/D, −1154G/A, and −634G/C polymorphisms was associated with 2.9-fold higher risk of PE. However, the placental IAG haplotype was associated with 0.3-fold lower risk of PE. In conclusion, the placental VEGF −2549 DD genotype was associated with severe PE and the placental −634GC and CC genotypes were associated with PE and severe PE. No association was found between VEGF −1154G/A polymorphism and PE or PE severity.

Association between Six CETP Polymorphisms and Metabolic Syndrome in Uyghur Adults from Xinjiang, China.

Objective: To explore the association between CETP gene polymorphisms and metabolic syndrome (MS), as well as the relationship between the CETP gene polymorphisms and each component of MS. Methods: A total of 571 individuals which were randomly selected from 5692 Uyghur adults were subdivided into two groups, including 280 patients with MS and 291 control subjects, using the group-matching method after matching for gender. We detected CETP polymorphisms (rs5882, rs1800775, rs3764261, rs12149545, rs711752, and rs708272) by using the Snapshot method. Results: (1) Significant differences were found involving the frequency distribution of genotypes and alleles of rs1800775, rs3764261, rs12149545, rs711752, and rs708272 between the control and MS groups (all p < 0.05). (2) rs1800775, rs3764261, rs12149545, rs711752, and rs708272 polymorphisms were significantly related to the risk of MS (all p < 0.05). (3) The rs1800775 polymorphism was associated with high fasting blood glucose levels and low high density lipoprotein cholesterol (HDL-C); rs3764261 and rs12149545 polymorphisms were associated with all components of MS except high blood pressure; rs711752 and rs708272 polymorphisms were associated with low HDL-C (all p < 0.05). (4) Complete linkage disequilibrium (LD) was identified for two pairs of single nucleotide polymorphisms (SNPs) (rs3764261 and rs12149545 (D’ = 1.000, r2 = 0.931), rs711752 and rs708272 (D’ = 1.000, r2 = 0.996)). (5) The A-G-G-G-C (p = 0.013, odds ratio [OR] = 0.622, 95% confidence interval [95% CI] = 0.427–0.906) and A-T-A-A-T (p < 0.001, OR = 0.519, 95% CI = 0.386–0.697) haplotypes were more frequent in the control group than in the case group. Conclusions: The rs1800775, rs3764261, rs12149545, rs711752, and rs708272 polymorphisms of CETP were associated with MS and its components among the Uyghur ethnic group. Complete LD was found between two pairs of SNPs (rs3764261 and rs12149545, rs711752, and rs708272). The A-G-G-G-C and A-T-A-A-T haplotypes might be protective factors for MS.

Rs3851179 Polymorphism at 5' to the PICALM Gene is Associated with Alzheimer and Parkinson Diseases in Brazilian Population.

Alzheimer's (AD) and Parkinson's diseases (PD) share clinical and pathological features, suggesting that they could have common pathogenic mechanisms, as well as overlapping genetic modifiers. Here, we performed a case-control study in a Brazilian population to clarify whether the risk of AD and PD might be influenced by shared polymorphisms at PICALM (rs3851179), CR1 (rs6656401) and CLU (rs11136000) genes, which were previously identified as AD risk factors by genome-wide association studies. For this purpose, 174 late-onset AD patients, 166 PD patients and 176 matched controls were genotyped using TaqMan® assays. The results revealed that there were significant differences in genotype and allele frequencies for the SNP PICALM rs3851179 between AD/PD cases and controls, but none for CR1 rs6656401 and CLU rs11136000 intronic polymorphisms. After stratification by APOE ε4 status, the protective effect of the PICALM rs3851179 A allele in AD cases remains evident only in APOE ε4 (-) carriers, suggesting that the APOE ε4 risky allele weakens its protective effect in the APOE ε4 (+) subgroup. More genetic studies using large-sized and well-defined matched samples of AD and PD patients from mixed populations as well as functional correlation analysis are urgently needed to clarify the role of rs3851179 in the AD/PD risk. An understanding of the contribution of rs3851179 to the development of AD and PDcould provide new targets for the development of novel therapies.

The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients

PurposeThe aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients.MethodsA total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 − 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays.ResultsThe patients with variant genotypes of VKORC1 − 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p < 0.001). Similarly, the patients with CYP2C9*3 variant allele required significantly lower warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 − 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability.ConclusionsVKORC1 − 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

Effect of PICALM rs3851179 polymorphism on the default mode network function in mild cognitive impairment

Alterations in default mode network (DMN) functional connectivity (FC) might accompany the dysfunction of Alzheimer’s disease (AD). Indeed, episodic memory impairment is a hallmark of AD, and mild cognitive impairment (MCI) has been associated with a high risk for AD. Phosphatidylinositol-binding clathrin assembly protein (PICALM) (rs3851179) has been associated with AD; in particular, the A allele may serve a protective role, while the G allele serves as a strong genetic risk factor. Therefore, the identification of genetic polymorphisms associated with the DMN is required in MCI subjects. In all, 32 MCI subjects and 32 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a genetic imaging approach. Subjects were divided into four groups according to the diagnosis (i.e., MCI and HCs) and the PICALM rs3851179 polymorphism (i.e., AA/AG genotype and GG genotype). The differences in FC within the DMN between the four subgroups were explored. Furthermore, we examined the relationship between our neuroimaging measures and cognitive performance. The regions associated with the genotype-by-disease interaction were in the left middle temporal gyrus (LMTG) and left middle frontal gyrus (LMFG). These changes in LMFG FC were generally manifested as an “inverse U-shaped curve”, while a “U-shaped curve” was associated with the LMTG FC between these four subgroups (all P<0.05). Furthermore, higher FC within the LMFG was related to better episodic memory performance (i.e., AVLT 20min DR, rho=0.72, P=0.044) for the MCI subgroups with the GG genotype. The PICALM rs3851179 polymorphism significantly affects the DMN network in MCI. The LMFG and LMTG may be associated with opposite patterns. However, the altered LMFG FC in MCI patients with the GG genotype was more sensitive to episodic memory impairment, which is more likely to lead to a high risk of AD.

Association between three VEGF polymorphisms and renal cell carcinoma susceptibility: a meta-analysis.

Several studies have reported an association between vascular endothelial growth factor (VEGF) gene polymorphisms rs2010963, rs3025039 and rs699947 and renal cell carcinoma (RCC). However, the results remain inconclusive and controversial. We therefore conducted a meta-analysis to evaluate this association. Electronic databases were searched for relevant case-control studies up to November 2016. RevMan 5.2 software and STATA version 12.0 were used for statistical analysis in our meta-analysis. Heterogeneity was assessed using the I2 value. Nine eligible studies were retrieved for detailed evaluation. The pooled estimates indicated that the GG genotype of VEGF rs2010963 polymorphism significantly decreased RCC risk [GG vs. GC+CC; GG vs. GC]. There was also a significant association between VEGF rs3025039 polymorphism and RCC susceptibility [CC+CT vs. TT; CC vs. TT]. Furthermore, a significant association between VEGF rs699947 polymorphism and RCC susceptibility was detected [A vs. C; AA+AC vs. CC; AA vs. AC+CC; AA vs. CC; AA vs. AC; AC vs. CC]. Subgroup analysis revealed that these associations held true especially for Asians. Our meta-analysis suggested that there may be a relationship between the VEGF rs2010963, rs3025039 and rs699947 polymorphisms and RCC susceptibility.

Intercellular adhesion molecule 1 rs5498 polymorphism is associated with the risk of myocardial infarction.

Several studies addressed the association between Intercellular adhesion molecule 1 (ICAM-1) rs5498 polymorphism and Myocardial Infarction (MI) risk. However, they addressed conflicting findings. Therefore, the aim of this study was to explore whether ICAM-1 gene rs5498 polymorphism plays an important role in modifying the risk of MI. A meta-analysis was conducted on the association between ICAM-1 rs5498 polymorphism and MI. 12 eligible studies involving 1,696 cases and 3,039 controls were included in the meta-analysis. Meta-analysis revealed that ICAM-1 rs5498 polymorphism showed a strongly positive correlation with MI and could be viewed as a protective factor for MI. Furthermore, subgroup analysis according to ethnicity indicated that ICAM-1 rs5498 polymorphism decreased the risk of MI among Caucasian and Asian populations. In conclusion, ICAM-1 rs5498 polymorphism was associated with the decreased risk of MI. Larger sample size studies with more diverse ethnic populations are needed to confirm these findings.

Whole transcriptome profiling of the human hippocampus suggests an involvement of the KIBRA rs17070145 polymorphism in differential activation of the MAPK signaling pathway

The rs17070145-T variant of the WWC1 gene, coding for the KIBRA protein, has been associated with both increased episodic memory performance and lowered risk for late onset Alzheimer's disease, although the mechanism behind this protective effect has not been completely elucidated. To achieve a better understanding of the pathways modulated by rs17070145 and its associated functional variant(s), we used laser capture microdissection (LCM) and RNA-sequencing to investigate the effect of rs17070145 genotypes on whole transcriptome expression in the human hippocampus (HP) of 22 neuropathologically normal individuals, with a specific focus on the dentate gyrus (DG) and at the pyramidal cells (PC) of CA1 and CA3 sub-regions. Differential expression analysis of RNA-seq data within the HP based on the rs17070145 genotype revealed an overexpression of genes involved in the MAPK signaling pathway, potentially driven by the T/T genotype. The most important contribution comes from genes dysregulated within the DG region. Other genes significantly dysregulated, and not involved in the MAPK pathway (Adj P < 0.01 and Fold Change > |1.00|) were: RSPO4 (HP); ARC, DUSP5, DNAJB5, EGR4, PPP1R15A, WBP11P1, EGR1, GADD45B (DG); CH25H, HSPA1A, HSPA1B, TNFSF9, and NPAS4 (PC). Several evidences suggested that the MAPK signaling pathway is linked with memory and learning processes. In non-neuronal cells, the KIBRA protein is phosphorylated by ERK1/2 (involved in the MAPK signaling) in cells as well as in vitro. Several of the other dysregulated genes are involved in memory and learning processes, as well as in Alzheimer's Disease. In conclusion, our results suggest that the effect of the WWC1 rs17070145 polymorphism on memory performance and Alzheimer's disease might be due to a differential regulation of the MAPK signaling, a key pathway involved in memory and learning processes.

The Importance of VEGF-KDR Signaling Pathway Genes should Not Be Ignored When the Risk of Developing Multiple Sclerosis is Taken into Consideration

Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) pathway trigger the process of angiogenesis as well as inflammation, which contributes to the development and progression of demyelinating lesions in multiple sclerosis. This work is a case-control study comprising of a total of 400 subjects with multiple sclerosis and 400 healthy controls. Participants were subjected to neurological examination and peripheral blood sampling for genotyping. Polymorphisms in the VEGF and KDR genes were assessed using the restriction fragment length polymorphism (RFLP-PCR) method. A significantly higher frequency of the T allele and TT genotype of the VEGF 936C>T (rs3025039) polymorphism was found in the multiple sclerosis group than in the healthy control group (P=0.01 [OR=1.41] and P=0.01 [OR=3.12], respectively). In addition, VEGF 936C > T showed an association with patients in a recessive model. However, the KDR -604T>C (rs2071559) polymorphism showed no significant difference in either allelic or genotype frequency between the two groups. Taken together, the results of the present study suggests that the T allele of the rs3025039 in VEGF gene could be considered a risk factor for developing multiple sclerosis in the Iranian population.

The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis.

BackgroundVascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study.Materials and methodsRelevant studies were collected systemically from the following three electronic databases: MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). Statistical analyses were performed using Review Manager 5.2 in a fixed- or random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to establish the strength of associations.ResultsA total of eight case–control studies with 1,936 RCC cases and 2,770 controls fulfilling the inclusion criteria were selected for this meta-analysis. The pooled OR indicated that rs699947 polymorphism was significantly associated with RCC risk in all genetic models. A significant association was also found between the rs3025039 polymorphism and RCC risk in a homozygous model (TT vs CC: OR =1.38, 95% CI =1.11–1.72, P=0.004), a dominant model (CT+TT vs CC: OR =1.21, 95% CI =1.05–1.39, P=0.01), and a recessive model (TT vs CC+CT: OR =1.28, 95% CI =1.04–1.57, P=0.02). After a subgroup analysis of ethnicity in the allele contrast model of rs3025039 polymorphism, we found a significant relationship in the allele contrast model (T vs C: OR =1.21, 95% CI =1.05–1.40, P=0.007) in the Asian population. With regard to rs10434 polymorphism, significant association was observed only in a homozygous model (GG vs AA: OR =0.75, 95% CI =0.57–0.98, P=0.03). As to rs1570360 or rs2010963, we did not observe any relationship between the two polymorphisms and RCC risk in our study.ConclusionOur meta-analysis confirmed the fact that rs699947, rs3025039, and rs10434 polymorphisms were significantly relevant to elevated RCC risk. In the meanwhile, this study also demonstrated that the allele contrast model of rs3025039 polymorphism was likely to be associated with risk of RCC in the Asian population.

Association between the Matrix Metalloproteinase-9 rs3918242 Polymorphism and Ischemic Stroke Susceptibility: A Meta-Analysis

In recent years, dozens of case-control studies showed that matrix metalloproteinase (MMP)-9 rs3918242 variants were associated with ischemic stroke (IS) susceptibility. However, the conclusions of case-control studies that evaluated the relationship between MMP-9 rs3918242 variants and the risk of IS were still equivocal. Herein, we conducted a comprehensive meta-analysis to investigate the association between MMP-9 rs3918242 variants and the risk of IS. We searched 5 databases (PubMed, EMBASE, Google Scholar, Web of Science, and Chinese Biomedical Literature Database) to identify the eligible studies up to October of 2016. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association of MMP-9 rs3918242 variants with IS susceptibility under the allelic model (T versus C) and the dominant model (TT + CT versus CC). A total of 14 studies with 3233 cases and 3123 controls were included in this meta-analysis. Our meta-analysis indicated that MMP-9 rs3918242 variants were associated with significantly increased risk of IS in overall populations (T versus C: OR = 1.43, 95% CI = 1.20-1.71, P < .001; TT + CT versus CC: OR = 1.39, 95% CI = 1.16-1.67, P < .001). Subgroup analysis based on ethnicity (Chinese and Caucasian) suggested that MMP-9 rs3918242 variants contributed to increase the risk of IS in Chinese population; However, no association was detected between MMP-9 rs3918242 variants and the risk of IS in Caucasian population. Therefore, our meta-analysis suggested that MMP-9 rs3918242 variants (T allele, TT and CT genotypes) contributed to significantly increase the risk of IS in the Chinese population.