ALOX5AP Gene Research Articles

Ferroptosis-Related APOE, BCL3 and ALOX5AP Gene Polymorphisms are Associated with the Risk of Thyroid Cancer.

PurposeThis study aimed to evaluate the association between polymorphisms in the ferroptosis-related genes apolipoprotein E (APOE), BCL3 transcription coactivator (BCL3) and arachidonate 5-lipoxygenase activating protein (ALOX5AP) and the risk of thyroid cancer.MethodsSix single nucleotide polymorphisms (SNPs) of APOE (rs429358 and rs7412), BCL3 (rs34698726 and rs8100239) and ALOX5AP (rs4076128 and rs4073259) were genotyped in 520 papillary thyroid carcinoma cases and 520 healthy controls using the MassARRAY platform.ResultsThe rs429358-TC, rs34698726-TA/TT, and rs8100239-AT/AA genotypes exhibited an elevated risk of thyroid cancer (prs429358 = 0.002, prs34698726 = 0.007, prs8100239 = 0.002), while rs7412-CT/TT and rs4076128-GA/GG were found to be protective genotypes against the risk of disease (prs7412 = 0.0003, prs4076128 = 0.0001). Genetic model analysis showed that APOE-rs429358 was correlated with an increased risk of disease under dominant and log-additive models (pdominant = 0.0004, plog-additive = 0.0006). BCL3-s34698726 and rs8100239 were associated with an elevated risk of disease under all three genetic models (p < 0.05). In contrast, APOE-rs7412 was related to a decreased risk of thyroid cancer under dominant and log-additive models (pdominant = 0.0001, plog-additive = 0.0001). Moreover, ALOX5AP-rs4076128 was also correlated with a reduced risk of disease under all three genetic models (p < 0.05).ConclusionThe results help us better understand how genetic polymorphisms in ferroptosis-related genes are relevant to thyroid cancer susceptibility.

Epigenetic regulation mechanism of DNA methylation and miRNAs on the expression of the ALOX5AP gene in patients with ischemic stroke.

5-lipoxygenase-activating protein (FLAP), encoded by the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene, can adjust the biogenesis of proinflammatory leukotrienes to increase the adhesion and permeability of the vascular internal wall. Moreover, it participates in the process of atherosclerosis and is closely associated with ischemic stroke (IS). Accumulating evidence has shown that the expression levels of the ALOX5AP gene are upregulated in patients with IS. However, the mechanism of ALOX5AP action in IS remain elusive. The present study hypothesized that epigenetic regulation, including DNA methylation and microRNA (miR/miRNA) regulation, affects the expression levels of the ALOX5AP gene. Therefore, 200 patients with a first diagnosis of acute IS and 200 healthy control subjects were enrolled in the present study. Initially, the mRNA expression levels of the ALOX5AP gene were examined by reverse transcription-quantitative PCR. It was found that the mRNA levels of ALOX5AP gene in the IS group were significantly higher compared with controls (P<0.05). Subsequently, the methylation status of 17 CpG sites located in the promoter region of ALOX5AP was assessed by MethyTarget sequencing. However, the levels of methylation exhibited no significant differences between IS and control groups (P>0.05). Moreover, the expression levels of miR-335 and miR-495 were examined as two potential miRNAs targeting the ALOX5AP gene. The expression levels of miR-335 and miR-495 in the IS group were significantly lower compared with the control group (P<0.05). Finally, the luciferase assay results indicated that the luciferase activity of the experimental group following co-transfection of miRNA mimic and wild-type reporter gene plasmid was significantly lower compared with the other experimental groups (P<0.05), suggesting that miR-335 and miR-495 could specifically bind to the 3'-untranslated region of the ALOX5AP gene, thereby downregulating its expression. The present study provided preliminary evidence demonstrating that epigenetic regulation affects the expression of the ALOX5AP gene in patients with IS.

The Role of Epigenetics in the Chronic Sinusitis with Nasal Polyp.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease. The underlying epigenetic mechanisms and treatment of CRSwNP are partially understood. Of the different epigenetic changes in CRSwNP, histone deacetylases (HDACs), methylation of DNA, and the levels of miRNA are widely studied. Here, we review the human studies of epigenetic mechanisms in CRSwNP. The promoters of COL18A1, PTGES, PLAT, and TSLP genes are hypermethylated in CRSwNP compared with those of controls, while the promoters of PGDS, ALOX5AP, LTB4R, IL-8, and FZD5 genes are hypomethylated in CRSwNP. Promoter hypermethylation suppresses the gene expression, while promoter hypomethylation increases the gene expression. Studies have shown the elevation in the levels of HDAC2, HDAC4, and H3K4me3 in CRSwNP. In CRSwNP patients, there is also an upregulation of certain miRNAs including miR-125b, miR-155, miR-19a, miR-142-3p, and miR-21 and downregulation of miR-4492. Epigenetics takes part in the immunology of CRSwNP and may give rise to endotypes of CRSwNP. Both HDAC2 and the miRNA including miR-18a, miR-124a, and miR-142-3p may take function in the regulation of glucocorticoid resistance. HDAC inhibitors and KDM2B have shown effectiveness in decreasing nasal polyp, and DNA methyltransferase (DNMT) or HDAC inhibitors may have a potential efficacy for the treatment of CRSwNP. Recent advances in the epigenetics of CRSwNP have led to the identification of several potential therapeutic targets for this disease. The use of epigenetics may provide novel and effective biomarkers and therapies for the treatment of nasal polyp.

The ALOXA5AP gene (rs38022789) is associated with diabetic nephropathy in Slovenian patients with type 2 diabetes mellitus.

Although the pathogenesis of diabetic nephropathy (DN) is multifactorial, and the precise mechanisms are unclear, there is a growing body of evidence suggesting that inflammatory processes and immune cells might be involved in the development and progression of DN. Leukotrienes (LTs) are a family of lipid mediators, which act as pro-inflammatory mediators. The study was designed to investigate the association between the polymorphism of the ALOX5 gene (rs12762303) and the ALOX5AP gene (rs3802278), and DN in patients with T2DM. 651 subjects with diabetes mellitus type 2 (T2DM) were classified into two groups according to the presence of DN, and tested for ALOX5 and ALOX5AP gene polymorphisms using the KASPar genotyping chemistry with validated assay. Biochemical analyses were performed using standard biochemical methods. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 3.14 higher risk for DN compared to TT genotype. Serum cystatin C was found to be statistically significantly higher in cases with DN in comparison with subjects without DN (p<0.001). An association between the rs3803278 of the ALOX5AP gene and DN was found in Slovenian patients with T2DM. The rs3803278 CC allele appears to confer increased risk of DN possibly by increasing the production of LTs-potent drivers of inflammation.

Relationship between Polymorphism in ALOX5, ALOX5AP and Susceptibility to Myeloid Leukemia

To investigate the correlation of single nucleotide polymorphisms (SNP) in arachidonate 5-lipoxygenase gene (ALOX5) rs2029253, rs2228064 and rs2228065 sites, 5-lipoxygenase activating protein gene (ALOX5AP) rs10507391, rs4769874 sites with the risk for genesis of adult myeloid leukemia. By the approval from the hospital ethics committee and the informed consent of participants. 150 patients with myeloid leukemia (ML) as ML group and 134 healthy people as the control group were selected. The genomic DNA was extracted from the samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with directly sequencing, PCR-amplified products were applied to test the polymorphism of 5 sites in ALOX5 and ALOX5AP gene. A allele frequencies of ALOX5 gene rs2029253 site in the ML group and the control group were 43.0% and 34.3%, respectively. And the G allele frequencies in the ML group and the control group were 57.0% and 65.7%, respectively. The genotype distributions of AA, AG and GG in ALOX5 gene rs2029253 site in the ML group were 32.2%, 21.5% and 46.3% respectively. That in the control group were 15.7%, 37.3% and 47.0% respectively. The genotype AA and A allele frequency of ALOX5 gene rs2029253 site were linked with the increased risk of myeloid leukemia (OR=2.26, 95% CI: 1.43-4.56, P＜0.05; OR=1.44, 95% CI: 1.02-2.03, P＜0.05). And the genotype AG and allele G reduced the susceptibility to myeloid leukemia (OR=0.46, 95% CI: 0.27-0.78, P＜0.01; OR=0.69, 95% CI: 0.50-0.98, P＜0.05), however, the polymorphisms of ALOX5 gene rs2228064 and rs2228065 site not correlated with the risk of myeloid leukemia (P＞0.05). The A allele frequency of ALOX5AP gene rs10507391 site in the ML group and the control group were 30.7% and 36.2% respectirely. The genotype distribution rates of AA, AT and TT in ALOX5AP gene rs10507391 site in the ML group was 1.3%, 58.7% and 40.0% respectively, that in the control group were 9.7%, 53.0% and 37.3% respectively. The genotype AA of ALOX5AP gene rs10507391 site correlated with the decreased risk of myeloid leukemia (OR=0.13, 95% CI: 0.03-0.57, P＜0.05), but the polymorphism of ALOX5AP gene rs4769874 site not correlated with the risk of myeloid leukemia (P＞0.05). The genotype AA, AG and allele A, G of ALOX5 rs2029253, as well as ALOX5AP rs10507391 may be correlate with the susceptibility to myeloid leukemia.

Relationship between Polymorphism in ALOX5, ALOX5AP and Susceptibility to Myeloid Leukemia

To investigate the correlation of single nucleotide polymorphisms (SNP) in arachidonate 5-lipoxygenase gene (ALOX5) rs2029253, rs2228064 and rs2228065 sites, 5-lipoxygenase activating protein gene (ALOX5AP) rs10507391, rs4769874 sites with the risk for genesis of adult myeloid leukemia. By the approval from the hospital ethics committee and the informed consent of participants. 150 patients with myeloid leukemia (ML) as ML group and 134 healthy people as the control group were selected. The genomic DNA was extracted from the samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with directly sequencing, PCR-amplified products were applied to test the polymorphism of 5 sites in ALOX5 and ALOX5AP gene. A allele frequencies of ALOX5 gene rs2029253 site in the ML group and the control group were 43.0% and 34.3%, respectively. And the G allele frequencies in the ML group and the control group were 57.0% and 65.7%, respectively. The genotype distributions of AA, AG and GG in ALOX5 gene rs2029253 site in the ML group were 32.2%, 21.5% and 46.3% respectively. That in the control group were 15.7%, 37.3% and 47.0% respectively. The genotype AA and A allele frequency of ALOX5 gene rs2029253 site were linked with the increased risk of myeloid leukemia (OR=2.26, 95% CI: 1.43-4.56, P＜0.05; OR=1.44, 95% CI: 1.02-2.03, P＜0.05). And the genotype AG and allele G reduced the susceptibility to myeloid leukemia (OR=0.46, 95% CI: 0.27-0.78, P＜0.01; OR=0.69, 95% CI: 0.50-0.98, P＜0.05), however, the polymorphisms of ALOX5 gene rs2228064 and rs2228065 site not correlated with the risk of myeloid leukemia (P＞0.05). The A allele frequency of ALOX5AP gene rs10507391 site in the ML group and the control group were 30.7% and 36.2% respectirely. The genotype distribution rates of AA, AT and TT in ALOX5AP gene rs10507391 site in the ML group was 1.3%, 58.7% and 40.0% respectively, that in the control group were 9.7%, 53.0% and 37.3% respectively. The genotype AA of ALOX5AP gene rs10507391 site correlated with the decreased risk of myeloid leukemia (OR=0.13, 95% CI: 0.03-0.57, P＜0.05), but the polymorphism of ALOX5AP gene rs4769874 site not correlated with the risk of myeloid leukemia (P＞0.05). The genotype AA, AG and allele A, G of ALOX5 rs2029253, as well as ALOX5AP rs10507391 may be correlate with the susceptibility to myeloid leukemia.

Association of 5-lipoxygenase activating protein gene polymorphism and stroke: A study from north east of Iran

Background: Stroke is a multifactorial disorder and a major cause of morbidity and mortality around the world. There are growing numbers of candidate gene pathways which are thought to be associated with stroke. Genes involved in lipid metabolism are important issues in stroke studies. Studying different polymorphisms in these genes are becoming an interest for researchers. 5-lipoxygenase activating protein (ALOX5AP) is one of these genes. Different studies have provided different relations between ALOX5AP promoter polymorphism (rs17222919) and stroke. In the present study, we have evaluated this gene polymorphism in a population in north east of Iran. Methods: This case-control study took place in Ghaem Hospital, Mashhad, Iran. Patients with computed tomography (CT) or magnetic resonance imaging (MRI) confirmation for ischemic stroke were enrolled in this study and considered as case group. Healthy persons without ischemic stroke were control group. During 1-year period of this study, ALOX5AP gene polymorphism in 200 healthy patients (control group) as well as 228 patients with stroke (case group) was evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: All of 428 persons (228 cases and 200 healthy controls) enrolled in this study. The genotype and allele frequency was significantly different between both groups (P = 0.001 and P = 0.003, respectively). A total number of 54 patients had G allele in case group in contrast to 27 ones in control group. Also, 174 patients in case group had T allele and 173 persons had this allele in control group. In compression of TT genotype, the risk of developing stroke in GG and TG genotypes increased by 3.998 and 1.643, respectively. Also the risk of ischemic stroke with G allele would increase by 2.128. Conclusion: According to our results, ALOX5AP promoter polymorphism (rs17222919) is related to increased ischemic stroke in Iranian population.

A clinical and genetic analysis of risk factors for the development of acute and chronic cerebral ischemia

To study the association between polymorphic markers in the ACE, SERPINE1, FGB, F5, F7, F12, GP1BA, GPIIIa, MTHFR, CYP11B2, PON1, PON2, NOS2, NOS2, HIFla, LTA, ALOX5AP genes and clinical characteristics of acute and chronic forms of circulatory disorders of the brain. MATERIAL AND METHODS: The analysis of polymorphic variants in ACE, FGB, F5, F7, F12, GP1BA, GPIIIa, SERPINE1, MTHFR, CYP11B2, PON1, PON2, NOS2, NOS3, PDE4D, HIF1a, LTA, ALOX5AP in 81 patients with chronic cerebral ischemia (CCI) and 69 patients with ischemic stroke (IS), and their interrelation with clinical manifestations of disease were investigated. RESULTS AND CONCLUSION: The association between the T/T genotype of the PDE4D SNP 83C>T polymorphism and a rapid progression of hypertensive disease (GB) was revealed (OR=6.22, CI=1.86-20.79, p=0.0036) in the group of patients with CCI. The association of the allele D and the DD genotype of the ACE (I>D, rs1799752) with cardioembolic stroke (OR=2.67, 95% CI=1.23-5.8, p=0.02 and OR=7.14, 95% CI=1.72-29.69, p=0.0057) was found. When comparing subgroups of patients with different degrees of stenosis of brachiocephalic arteries (BCA), the association of the allele C and the TC genotype of the GP1BA (rs2243093, -5T/C) with BCA occlusion and expressed hemodynamically significant stenosis (>75%) was revealed (OR=3.39, 95% CI=1.12-10.25, p=0.03 and OR=4.44, 95% CI=1.27-15.54, p=0.023, respectively). Thus, polymorphic markers in PDE4D, ACE, GP1BA in combination with certain clinical characteristics are risk factors for the progression of CCI and development of IS.

Interstitial lung disease in Systemic sclerosis: insights into pathogenesis and evolving therapies.

Interstitial lung disease (ILD) is a leading cause of mortality in systemic sclerosis (SSc). However, mortality is improving as pathogenesis is being better understood and new therapies emerge. The roles of the inflammasome and NETosis in fibrosis are being elucidated. Epigenetic targets like DNA methylation and microRNA show promise as new targets for anti-fibrotic agents. The IL17-23 pathway has been shown to be active in SSc-ILD. Newer biomarkers are being described like CCL18 and the anti-eIF2B antibody. Hypothesis-free approaches are identifying newer genes like the ALOX5AP and XRCC4 genes. Computer-aided interpretations of CT scans, screening with ultrasonography and magnetic resonance imaging (MRI) are gradually emerging into practice. Imaging can also predict prognosis. A plethora of studies has shown the benefit of immunosuppression in halting ILD progression. Extent of lung involvement and PFT parameters are used to initiate therapy. The best evidence is for cyclophosphamide and mycophenolate. Besides these, corticosteroids and rituximab are being used in cases refractory to the first line drugs. Stem cell transplant is also backed by evidence in SSc. Longer studies on maintenance therapy are awaited. The inflammation in SSc is mostly subclinical and there is great interest in developing anti-fibrotic drugs for SSc-ILD. Perfinidone and nintedanib are under trial. The last resort is lung transplantation.

Allele-specific methylation contributed by CpG-SNP is associated with regulation of ALOX5AP gene expression in ischemic stroke.

Previous studies have shown that CpG-SNPs might have influence on gene function via allele-specific DNA methylation (ASM). However, association study between DNA methylation and the promoter CpG-SNPs in ALOX5AP gene with IS has not been reported. The present study aims to explore the relationship among CpG-SNPs, methylation levels, and messenger RNA (mRNA) expression levels of ALOX5AP gene. Firstly, we made a two-stage association study to identify a potential associated CpG-SNP (rs4073259) by SNaPshot genotyping approach (P = 0.015, OR = 0.672, 95% CI 0.487-0.927; P = 0.035, OR = 0.809, 95% CI 0.664-0.985, respectively). In addition, the methylation levels of 17 CpG sites located in the promoter of ALOX5AP were tested by MethylTarget sequencing. The methylation level of GG genotype carriers is significantly higher than those with the AG and AA genotypes (P < 0.05). And the GG genotype carriers with higher DNA methylation levels have a decreased mRNA expression levels of ALOX5AP (P < 0.05). Finally, we found that the G allele with higher methylation level has got a lower transcription activity than the A allele by luciferase assay (P = 0.000).The study provided evidence that IS-associated CpG-SNP rs4073259 may affect the expression level of ALOX5AP through allele-specific methylation and consequently the phenotype of the disease.

Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus.

Inflammation plays a pivotal role in the pathogenesis of diabetes and its complications. Arachidonic acid lipoxygenases have been intensively studied in their role in inflammation in metabolic pathways. Thus, we aimed to explore variants of lipoxygenase genes (arachidonate lipoxygenase genes) in a diabetes adult population using a case-control study design. Study population consisted of 1285 elderly participants, 716 of whom had type 2 diabetes mellitus. The control group consisted of non-diabetes individuals with no history of diabetes history and with a glycated haemoglobin <6.5% (<48 mmol/mol)] and fasting plasma glucose levels <126 mg/dL. Blood samples were genotyped on Illumina Infinium PsychArray. Variants of ALOX5, ALOX5AP, ALOX12, ALOX15 were selected. All statistical analyses were undertaken within PLINK and SPSS packages utilising permutation analysis tests. Our findings showed an association of rs9669952 (odds ratio = 0.738, p = 0.013) and rs1132340 (odds ratio = 0.652, p = 0.008) in ALOX5AP and rs11239524 in ALOX5 gene with disease (odds ratio = 0.808, p = 0.038). Rs9315029 which is located near arachidonate ALOX5AP also associated with type 2 diabetes mellitus ( p = 0.025). No variant of ALOX12 and ALOX15 genes associated with disease. These results indicate a potential protective role of ALOX5AP and 5-arachidonate lipoxygenase gene in diabetes pathogenesis, indicating further the importance of the relationship between diabetes and inflammation. Larger population studies are required to replicate our findings.

P3247Polymorphisms of the ALOX5AP gene (5-lipoxygenase activating protein) are associated with increased cardiovascular risk in patients with acute coronary syndrome: Analysis of PLATO genetics sub-study

P3247Polymorphisms of the ALOX5AP gene (5-lipoxygenase activating protein) are associated with increased cardiovascular risk in patients with acute coronary syndrome: Analysis of PLATO genetics sub-study

The SG13S114 polymorphism of the ALOX5AP gene is associated with ischemic stroke in Europeans: a meta-analysis of 8062 subjects.

The association between ALOX5AP SG13S114 polymorphism and ischemic stroke (IS) susceptibility has extensively been investigated, especially in white populations; however, the results were inconclusive. Here, we perform a meta-analysis to clarify the effect of SG13S114 variant on the IS risk in Europeans. The Web of Science, PubMed, EMBASE, and Medline were searched up to August 1st, 2016. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model. In total, 8 case control studies involved 8062 subjects were finally included in this meta-analysis. We observed a significantly decreased IS risk in persons carrying an A allele at the SG13S114 polymorphism compared with those with a T allele (A vs T, OR=0.856, 95% CI=0.797-0.919, p<0.001). In addition, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. In addition, the publication bias was not detected using the funnel plot and Egger's tests. In summary, the present meta-analysis suggested that the A allele at the ALOX5AP SG13S114 polymorphism is a protective factor for the IS in the Europeans. In addition, further studies with large sample size are needed to validate the association, as well as in other ethnic groups.

Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic Interactions in a Chinese Population

Background/Aims: To investigate the roles of the oxidative stress related-genes ALOX5, ALOX5AP and MPO in ischemic stroke susceptibility in the Han Chinese population. Methods: A total of 351 ischemic stroke patients and 417 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 gene polymorphisms were genotyped. Results: We identified that rs2107545 of MPO gene was significantly associated with ischemic stroke susceptibility after adjusting for covariates. Furthermore, we also considered the likely complexity of oxidative stress and inflammatory process in stroke by assessing the combined effects of multiple genes. Generalized multifactor dimensionality reduction (GMDR) analysis revealed that the combination of ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 was significantly associated with increased risk of ischemic stroke (P=0.0040, OR (95% CI) =1.991 (1.241 to 3.195)). Additionally, the MPO rs2107545 genotype was significantly associated with clinical outcomes at 6 months after discharge from the hospital. Conclusion: Our study revealed that epistatic interaction among the ALOX5, ALOX5AP and MPO genes played a significant role in vulnerability to ischemic stroke. Furthermore, these results also suggest that the rs2107545 of MPO gene can be used as a biomarker for the susceptibility and prognosis of ischemic stroke patients.

Genetic Variants in the Transcriptional Regulatory Region of the ALOX5AP gene and Susceptibility to Ischemic Stroke in Chinese Populations.

No coding sequence variants of the ALOX5AP gene that lead to amino acid substitutions have been identified. A two-stage study design was used to explore the relationship between variants in the transcriptional regulatory region of ALOX5AP gene and ischemic stroke (IS) risk in Chinese populations. IS was determined using CT and/or MRI. First, 18 SNPs, located in the upstream promoter region of ALOX5AP gene, were genotyped in 200 IS patients and 200 controls. And one potential associated SNP (rs17222919) was identified (P = 0.005,OR = 0.623, 95% CI: 0.448~0.866). Next, another independent case-control cohort comprising 810 IS patients and 825 matched controls was recruited to investigate the role of rs17222919, rs9579646 polymorphisms and their haplotypes in IS risk. The G allele frequency of rs17222919 in the IS group was significantly lower than that in control group (P = 0.007, OR = 0.792, 95% CI: 0.669~0.937). T-A and G-A haplotypes were associated with IS (P = 0.001,OR = 1.282, 95% CI:1.100~1.495; P = 0.0001, OR = 0.712, 95% CI: 0.598~0.848; respectively). Our study providesevidence that rs17222919 is a potential genetic protective factor against IS. Furthermore, the T-A haplotype is a risk factor and the G-A haplotype is a protective factor against IS in Chinese population.

Genetic polymorphisms of T-1131C APOA5 and ALOX5AP SG13S114 with the susceptibility of ischaemic stroke in Morocco.

Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammatory and thrombotic metabolisms play an important role in the development of ischaemic stroke. The present study aimed to assess the relationship between T1131C APOA5 and SG13S114 ALOX5AP polymorphisms and the risk of ischemic stroke in 175 cases and 201 controls. Genotyping was performed by high resolution melting and polymerase chain reaction restriction fragment length polymorphism methods. In the case of T-1131C APOA5, a modest risk of ischaemic stroke was noticed with CC (OR: 2.86; 95% CI = 1.24-6.58; Pc = 0.039) and C allele (OR: 1.54; 95% CI = 1.01-2.33; Pc = 0.014). For SG13S114 ALOX5AP, a significant association was observed among subjects with TT (OR: 2.57; 95% CI =1.49-4.83; Pc = 0.009) and T allele (OR: 1.59; 95% CI = 1.16-2.19; Pc = 0.008). According to the risk factors of ischaemic stroke, a positive correlation was observed only between SG13S114 variant of ALOX5AP gene and hypertension (Pc = 0.026). Despite lower sample size, T-1131C APOA5 and SG13S114 variants could be considered an independent genetic risk factor of ischaemic stroke in Moroccan population.

Implementation analyses of proteins and genes obtained from cancer patients

bioinformatics and computational molecular biology, since these studies may result in important results in the case of diseases. Due to this, in this study, bioinformatics data were analyzed based on nucleotides and motifs. Bioinformatics data for proteins were obtained from two different databases. The obtained data belonged to cancer patients, and the genes in these DNA and protein sequences, the proteins synthesized by these sequences, and motifs in these data were analyzed. In the analysis, the ABCB1, ALOX5AP, AKT1, BRCA1, BRCA2, TNF, TNFSF13B, TP53, TP63, TP73, and WT1 genes were used. The proteins synthesized by genes belonging to similar classes were analyzed based on amino acid distributions, atomic distributions, Ramachandran plot similarities, and motifs.

Variants in the Atherogenic ALOX5AP, THBD, and KNG1 Genes Potentiate the Risk of Ischemic Stroke via a Genetic Main Effect and Epistatic Interactions in a Chinese Population

Ischemic stroke (IS) is a multifactorial disease that displays a strong genetic predisposition. However, the genetic architecture of IS has yet to be fully elucidated. It was hypothesized that epistasis between genes in multiple atherothrombotic pathways may play a vital role in determining the susceptibility to IS. The aim of the present study was to investigate the contributions of the hypothesized genetic factors to IS and the interactions between these genetic factors in a Chinese population. In this study, 351 cases with IS and 417 control subjects from a Chinese population were genotyped for single-nucleotide polymorphisms (SNPs) in 12 genes hypothesized to be involved in atherosclerosis, coagulation, and related pathways. We examined SNP main effects and epistatic interactions between these polymorphic loci. rs710446 of the KNG1 gene was associated with IS susceptibility based on an additive genetic model (rs710446: P = .012; odds ratio [OR], 1.247; 95% confidence interval [CI], 1.050-1.481) after adjusting for covariates. Furthermore, an epistatic interaction between the ALOX5AP, THBD, and KNG1 gene was also identified in association with stroke susceptibility (P < .001 after 1000 permutations). Based on the chi-squared test, the OR of the high-risk combination of the three-locus model increased the risk of IS by 2.53-fold (95% CI, 1.60-4.01; P < .0001). Our findings support the association of the epistatic interactions of ALOX5AP, THBD, and KNG1 and present novel evidence for the main effect of KNG1 gene on IS susceptibility, suggesting a modulation of stroke risk by a genetic main effect and gene-gene interactions.

A promoter polymorphism (rs17222919, -1316T/G) of ALOX5AP gene is associated with decreased risk of ischemic stroke in two independent Chinese populations.

No coding sequence variants of the gene encoding 5-lipoxygenase-activating protein (ALOX5AP) leading to amino acid substitutions have been identified. Therefore, variants in the ALOX5AP promoter region have received attention recently. The purpose of this study was to explore whether the promoter polymorphism rs17222919 is involved in the etiology of ischemic stroke (IS) in the Chinese Han population. We investigated the rs17222919 polymorphism by TaqMan genotyping in two independent Chinese Han samples: the first comprised 910 IS patients and 925 healthy inhabitants from the northern Henan Province, while the second included 1003 IS patients and 889 healthy controls from the southern Henan Province. Functional characterization of rs17222919 was performed by an in vitro luciferase assay. After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.675–0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668–0.915, respectively). This was also observed in the large-artery atherosclerosis (LAA) and stroke of other undetermined etiology (SUE) subtypes (P = 0.019, OR = 0.815, 95% CI = 0.687–0.967; P = 0.021, OR = 0.815, 95% CI = 0.685–0.970, respectively). Additionally, the TG genotype and G allele frequencies were significantly lower in the IS compared with the control group in two female cohorts (P<0.05). Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031). Our study provides evidence that the promoter single nucleotide polymorphism (SNP) rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.

Interrelationships between ALOX5AP polymorphisms, serum leukotriene B4 level and risk of acute coronary syndrome.

BackgroundWe investigated the relationships between the ALOX5AP gene rs10507391 and rs4769874 polymorphisms, serum levels of leukotriene (LT) B4, and risk of acute coronary syndrome (ACS).MethodsA total of 709 participants, comprising 508 ACS patients (ACS group) and 201 noncoronary artery disease patients with chest pain (control group) were recruited from the Han population of the Changwu region in China. Two polymorphic loci were genotyped using polymerase chain reaction and restriction fragment length polymorphism analysis. Serum LTB4 level was determined by enzyme-linked immunosorbent assay.ResultsSerum LTB4 levels were significantly higher (P<0.001) in the ACS group (median/interquartile range, 470.27/316.32 pg/ml) than in the control group (233.05/226.82 pg/ml). No statistical differences were observed between genotype, allele and haplotype frequencies for the tested loci in either the ACS group or the control group, even after adjustments were made for conventional risk factors by multivariate logistic regression. This suggests there is no association between the ALOX5AP rs10507391 and rs4769874 polymorphisms and ACS risk. Elevated serum LTB4 level was closely linked to ACS risk, and may be independent of traditional risk factors as a risk factor for ACS (P<0.001). There was no significant association between serum LTB4 levels and the two variants in either the ACS group or the control group.ConclusionsRs10507391, rs4769874 and its haplotypes in ALOX5AP are unrelated to ACS risk in the Chinese Han population of Changwu, but elevated serum LTB4 level is strongly associated with ACS risk. Serum LTB4 level is not subject to the influence of either the rs10507391, rs4769874 or the haplotype.