Frequency Of TT Genotype Research Articles

PB2406 THE INFLUENCE OF XMNI AND BCL11A GENE MODIFIERS ON HEMOGLOBIN F LEVELS IN EGYPTIAN β‐THALASSEMIA MAJOR PATIENTS

Background:β‐thalassemia major (β‐TM) is an autosomal recessive disorder in which β‐globin chain synthesis is severely decreased or absent which lead to blood transfusion dependency with its catastrophic complications. Polymorphisms at position ‐158 of XmnI‐HBG2 on chromosome 11 and BCL11A site on chromosome 2p16 might be associated with elevated hemoglobin F (HbF) expression which may,in turn,improve β‐thalassemia severityAims:This study aims to explore the modifying effects of XmnI and BCL11A loci on HbF levels in Egyptian β‐thalassemia patientsMethods:A prospective case‐control study of 70 multi‐transfused β‐thalassemia major patients and 22 controls was conducted in Paediatric hematology unit of Assiut university hospital from January 2016 till April 2017. PCR‐RFLP was used for detection of single nucleotide polymorphisms at XmnI and BCL11A site loci.Results:XmnI Polymorphism detected in 9 of 70 patients and associated with higher mean HbF levels (53.48%) than patients without polymorphism (meanHbF level was 42.23%)(P‐Value = 0.035).The frequency of CT heterozygousgenotype was 8(11.4%), TT homozygous genotype was (1.4%) while the wild genotype CC detected in 61 (87.1%) of the cases. While BCL11A Polymorphism detected in 21 of 70 patients had no effect on either Hb or HbF levels (P‐Value = 0.26). The TT genotype frequency was 49 (70%) and TC heterozygous genotype was detected in 21 (30 %) of patients. The CC genotype was absent.Summary/Conclusion:The presence of XmnI polymorphism rather than BCL11A polymorphism has a modifying effect on HbF production and increased Hb levels between β‐TM patients and so, it helps in identifying patients’ benefits from HU therapy.image

Interleukin-1β Gene (IL1B) Polymorphism and Risk of Developing Diabetic Nephropathy

ABSTRACTObjective: Cytokines play an important role in the pathogenesis of type 2 diabetes (T2DM) and its complications. The aim of the study was to evaluate an association of the −511 (C/T) polymorphism in the IL1B gene with diabetic nephropathy (DN).Methods: The study population included 860 patients with T2DM (506 with diabetic nephropathy and 354 without nephropathy) as well as 505 healthy individuals. Genomic DNA was genotyped for the IL1B −511 (C/T) polymorphism using PCR-RFLP technique.Results: The IL1B −511 C/T polymorphism was genotyped in 860 T2DM patients with or without DN and 505 healthy individuals. The average age of patients was 65.3 years in DN+ and 62.2 years in DN- subgroups. The genotype distribution did not differ significantly between patients and controls. Only a tendency to a slight increase of T allele frequency was observed in patient group. Genotype and allele frequencies of −511 C/T polymorphism were compared in patients with DN and those without it. The minor allele (T) and homozygote TT frequencies were significantly different between subgroups. The T allele was more frequent in DN+ patients, with odds ratio 1.45 (95% CI 1.2–1.8), p = 0.0003. The TT genotype frequency was also higher in DN+, with OR 1.76 (96% CI 1.1–2.7), p = 0.01.Conclusion: In a studied population the −511 C/T polymorphism in the IL1B gene is associated with diabetic nephropathy in dialyzed T2DM patients. Further studies are required to confirm the clinical significance of this finding.

Association of 584C/T polymorphism in endothelial lipase gene with risk of coronary artery disease.

Coronary artery disease (CAD) is one of the cardiovascular diseases, which is caused by a reduced amount of oxygen and blood that goes to the heart. CAD includes stable angina, unstable angina, myocardial infarction, and sudden cardiac death. It is a common cause of death in both men and women. The environmental and genetic factors are involved in the development of CAD. Multiple gene polymorphisms are risk factors of CAD. To evaluate the association between EL 584C/T polymorphism, CAD risk, and lipid profile in an Egyptian population. This is a case-control study. The patients were classified into three groups: Group A: Control group, this group included 42 apparently healthy people. Group B: included 42 subjects diagnosed with previous myocardial infarction (MI). Group C: included 42 subjects diagnosed with unstable angina (UA). The frequencies of TT and CT genotypes and T allele were higher in control healthy individuals than CAD patients. In addition, the risk of CAD was significantly lower in individuals carrying T allele (P = 0.001). Serum high-density lipoprotein (HDL) levels were significantly higher in healthy individuals and CAD patients (MI and UA patients) carrying EL 584 T allele compared with those carrying CC genotype (P ≤ 0.001). By multiple logistic regression, we found that the protective effect of T allele remained significant (P = 0.005) and it decreased the risk of CAD independent of plasma HDL levels. There was a significant difference between 584C/T polymorphism in the EL gene and CAD and HDL level. T-allele carriers had a higher HDL level and were protected from CAD. T allele was significantly associated with the decreased risk of CAD independent of plasma HDL levels.

FOXO3a gene polymorphism and bronchial asthma in Egyptian children INTRODUCTION Bronchial asthma is the most prevalent chronic immunological disorder in childhood period. It is characterized by airways inflammation and bronchial hyper-responsiveness where

Background: FOXO3a proteins play multiple crucial roles in immune response. FOXO3 inhibits T cell proliferation, induces T cell apoptosis via upregulation of proapoptotic proteins and it suppresses T cell activation preventing autoimmunity. The role of FOXO3a gene in the pathogenesis of bronchial asthma has been studied in few ethnic groups and revealed its implication in asthma pathogenesis. Objectives: The aim of the current study is to detect the association between single nucleotide polymorphism of the FOXO3a gene (rs13217795) and bronchial asthma, atopy and asthma severity in Egyptian children. Methods: The current cross-sectional case-control study was performed on 75 asthmatic children aged 2 to 12 years following up in the pulmonology outpatient clinic in Children's hospital, Cairo University and 75 age and sex matched healthy controls. Candidates were subjected to clinical evaluation in addition to genotyping for the FOXO3a gene polymorphism using PCR-RFLP technique. Results: The highest frequency was for the heterozygous type CT in both cases and controls groups. The genotype frequencies of mutant type TT for cases and controls were 12 % and 16% respectively, and the T allele frequencies were 37.2% in cases and 46.7% in the control group while CC genotype was present in 37.3% of asthmatic patients and 22.6% in the controls and the C allele was detected in 62.8% and 53.3% for cases and controls respectively. No statistically significant differences were observed between asthmatic patients and controls regarding the different genotypes of the FOXO3a gene polymorphism (p=0.161). No significant association was detected between the different genotypes of the FOXO3a gene polymorphism and the atopic status (p=0.536) or the different grades of asthma severity (p= 0.545). Conclusions: The study of FOXO3a gene polymorphism (rs13217795) in asthmatic Egyptian children revealed low frequency of the mutant TT genotype among cases and controls. In the current study, FOXO3a polymorphism has no role in the pathogenesis of asthma or atopy. Moreover, it has no relation to degree of disease severity. Keywords: Asthma, FOXO3a, gene, children, Egyptian, polymorphism

MTHFR C677T Polymorphism Is Associated with the Risk of Breast Cancer among Kurdish Population from Western Iran

Background: The key enzyme of methylenetetrahydrofolate reductase (MTHFR) is involved in DNA biosynthesis and repair. Objectives: The role of MTHFR C677T polymorphism in susceptibility to breast cancer is controversial. Methods: In the present case-control investigation, 297 individuals consisted of 100 patients with breast cancer and 197 healthy women were studied for MTHFR C677T genotypes, using PCR-RFLP method. Results: The frequency of MTHFR TT genotype was 10% in patients and 3% in controls (P = 0.008). The presence of TT genotype was associated with susceptibility to breast cancer [OR = 1.97, 95%CI: 1.16-3.36, P = 0.012]. The T allele of MTHFR was found in 30% of the patients compared to 27.6% healthy controls (P = 0.024) that enhanced the risk of breast cancer by 1.56 times (95% CI: 1.06 - 2.3, P = 0.024). There were 71 individuals (71%) with the age of breast cancer diagnosis ≤ 51 years old. Comparing patients with the age of cancer diagnosis ≤ 50 years old with those > 51 years old group indicated a higher frequency of MTHFR TT genotype in the latter (20.7%) compared to the first group (5.6%, P = 0.05). Conclusions: Our study demonstrated an association between the MTHFR C677T polymorphism with the risk of breast cancer among population of Western Iran. Also, our study suggests that the MTHFR TT genotype could be a risk factor for breast cancer in postmenopausal women.

Association study of the CTH 1364 G>T polymorphism with coronary artery disease in the Greek population.

Background Cystathionine γ-lyase enzyme, which is encoded by the CTH gene, is responsible for hydrogen sulfide (H2S) production in the endothelium. The CTH 1364 G>T polymorphism may alter the CTH expression and H2S bioavailability, thus leading to atherosclerosis and coronary artery disease (CAD). We examined the potential association of the CTH 1364 G>T polymorphism with CAD. Methods The CTH 1364 G>T polymorphism was determined in 178 coronary artery bypass grafting (CABG) patients and 156 non-atherosclerotic controls of Greek Caucasian origin using the PCR-RFLP method. Results No significant difference in the frequency of the CTH 1364 G>T genotypes (p = 0.281) and alleles (p = 0.265) was found between the CABG patients and controls. After conducting stratification according to sex, analysis showed a numerical difference in the CTH 1364 TT genotype frequency in female participants that did not reach statistical significance (16.3% and 8.5% in the CABG and controls, respectively, p = 0.26). The frequency of the CTH 1364 TT genotype between the male CABG patients and controls did not differ (p = 0.507). Conclusions The CTH 1364 G>T polymorphism was not associated with CAD in the studied population. However, interestingly, a higher - if not significantly so - CTH 1364 TT genotype frequency was present in female CABG patients compared with female controls. Larger studies are necessary to conclude on the potential overall or gender-driven association between CTH 1364 G>T gene polymorphism and CAD.

Association between lncRNA IFNG-AS1 SNP and Hashimoto′s thyroiditis

Objective To assess the association between three single nucleotide polymorphisms(SNPs)(rs10878724、rs7980829 and rs11177020) of lnc IFNG-AS1 and Hashimoto′s thyroiditis(HT) susceptibility. Methods TaqMan probe technology was used to genotype the selected SNPs in a total of 179 subjects, including 70 HT cases, and 109 controls. The expression levels of lnc IFNG-AS1 and IFNG were detected by SYBR-Green qRT-PCR. Results Compared with control, not only the A allele and AA genotype frequencies of rs10878724 were significantly different in group HT(P=0.01, P=0.003), but also the T allele and TT genotype frequencies of rs7980829 were significantly high in group HT. Haplotype analysis showed that the G-G-A decreased the risk of HT(P=0.04), while the haplotype of A-T-T incresed the risk of HT(P=0.01). The relative expression of both IFNG mRNA and lnc IFNG-AS1 were higher in group HT than in control(P=0.001, P=0.013). In HT patients, IFNG mRNA relative expression in both rs7980829-TT and rs1087872-TT were significantly higher than those of other genotypes(P=0.017, P=0.009). Conclusion The SNPs of Inc IFNG-AS1 were correlated with the expression levels of IFNG and lncRNA IFNG-AS1. Noncoding genes should be further screened as potential biomarkers in prediction of HT susceptibility. Key words: IFNG gene; IFNG-AS1; Long non-coding RNA; Single nucleotide polymorphisms; Hashimoto thyroiditis

Correlations of Calcium Voltage-Gated Channel Subunit Alpha1 A (CACNA1A) Gene Polymorphisms with Benign Paroxysmal Positional Vertigo.

BackgroundThe aim of this study was to investigate the correlations of calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene polymorphisms with benign paroxysmal positional vertigo (BPPV).Material/MethodsA total of 120 BPPV patients and 60 healthy controls were enrolled according to the diagnostic criteria in the Guideline of Diagnosis and Treatment of Benign Paroxysmal Positional Vertigo (2017). Clinical and biochemical data were collected, the rs2074880 (T/G) polymorphisms in the CACNA1A gene were detected using TaqMan-MGB probe method, and the correlations of BPPV with predisposing factors were analyzed through logistic analysis.ResultsThe BPPV group had higher levels of cholesterol and uric acid than in the control group (p<0.05). The cholesterol and uric acid levels were positively correlated with BPPV (p<0.05) [odds ratio (OR)=2.298 (1.252–4.350), 95% confidence interval (95% CI)=1.123 (0.987–1.987)]. The distribution frequency of TT genotype was higher than that of GG genotype (χ2=9.907, p=0.002, OR=0.279, 95% CI=0.123–0.633). In the BPPV group, cholesterol and uric acid levels of TT genotype were elevated compared with those in GG genotype (p<0.05).ConclusionsThe onset of BPPV is related to the increased levels of cholesterol and uric acid, as well as the dominant homozygous mutation of rs2074880 (T/G) in the CACNA1A gene.

Association of Pro198Leu polymorphism in glutathione peroxidase one (GPX1) gene with peripheral neuropathy in type 2 diabetic patients.

To evaluate the association of Pro198Leu polymorphism in glutathione peroxidase 1 gene in type 2 diabetic patients with neuropathy. The comparative cross-sectional study was conducted from February 2 to November 30, 2018, at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Neurology, Military Hospital, Rawalpindi. Diagnosed type 2 diabetics of either genders aged 40-70 years were divided into two equal groups of neuropathy and non- neuropathy subjects. Deoxyribonucleic acid was subjected to restriction fragment length polymorphism for glutathione peroxidase 1gene analysis. Hardy Weinberg equation was used to check the genotype frequency equilibrium. Of the 60 patients, there were 30(50%) each in the two groups. Age, fasting glucose level and diabetes duration were significantly different between the groups (p<0.05). Even though the frequency of TT genotype was higher, no association of the polymorphism and any of the genotypes was found with diabetic neuropathy (p>0.05). There was no association found between Pro198 Lue polymorphism in glutathione peroxidase 1 and diabetic neuropathy.

Involvement of KRAS rs61764370 T&gt;G Gene Variation in Leukemia Patients of Saudi Arabia

Background: Recently, a variant allele in the 3?UTR of the KRAS gene (rs61764370 T>G) was shown to be associated with an increased risk for developing multiple cancer types like lung ,ovarian and breast cancer .Therefore, we investigated the association of KRAS (rs61764370 T>G) gene variation in leukemia susceptibility in our population. Methodology: This population-based case–control study was done on 72 clinically confirmed Leukemia patients and 87 matched healthy controls with no history of any type of cancer. The KRAS rs61764370T>G genotyping was detected by using Allele specific PCR. Results: We observed a statistically significant difference in the frequencies of KRAS TT, GT and TT genotypes among patients and healthy controls (p=0.0271).This study reported significantly higher percentage of TT (11%) ,GT (75%) and GG (14%) genotypes in patients compared to controls TT (25%) ,GT (69%) and GG (06%) genotypes while higher percentage of GG (14%) genotype were reported in patients compared to control GG (6%) genotypes .Our findings showed that the KRAS rs61764370 T>G variant was associated with an increased risk of Leukemia in codominant inheritance model (OR=5.5, 95%CI= (1.43-21.0); RR=2.20, (1.04-4.64), p=0.038 TT vs GG. Dominant inheritance model (OR=2.70, 95% CI= (1.21-6.52): RR=1.45(1.10-1.91), P=0.007 (TG+ GG) VS TT and Recessive inheritance model (OR=2.64, 95%CI= (0.86-8.13), RR (1.70(0.82-3.54) P=0.025 (GG vs TT+GT) tested. While, the G allele significantly increased the risk of Leukemia (OR= 1.57; 95% CI= (1.03-2.45); RR 1.22(0.99-1.51) P=0.047 compared to T allele. Conclusion: Our findings indicated that KRAS rs61764370 GG genotype and G allele are associated with an increased susceptibility to leukemia in Saudi Arabian population. It can be used as a predisposing genetic marker for Leukemia .Furthers studies with larger sample sizes are necessary to confirm our findings.

Peroxisome Proliferator Activated Receptor (PPAR) Delta Genetic Polymorphism in Saudi Normal Population

Background: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the superfamily of nuclear hormone receptors. Three PPARs members, PPAR-alpha, PPAR- delta and PPAR gamma, have been characterized. PPAR-delta in humans is encoded by the PPARD gene and has been shown to possess a role in regulating fatty acid catabolism and energy homeostasis. Several polymorphisms have been identified in PPARD as potential functional variants. PPARD +294T > C polymorphism was shown to modify serum lipid concentrations in some ethnic groups. Aim: The current study aimed to screen the presence of the PPARD polymorphism in the Saudi population. Method: Blood samples were collected from normal individuals. Genomic DNA was extracted from peripheral blood monnuclear cells and the partial gene of the PPARD was amplified by polymerase chain reaction and subjected to gel electrophoresis. PPARD rs2016520 polymorphism was analyzed by polymerase chain reaction–restriction fragment length polymorphism. Results: The frequencies of CC, CT, and TT genotypes in normal Saudi population were 9.09%, 14.2% and 76.6%, respectively. Conclusion: The Saudi nationals seems to have low frequency of the PPARD +294T > C polymorphisms. Limitations: Relatively small sample size, serum lipid levels were not determined.

DNA variants in Helicobacter pylori infected patients with chronic gastritis, dysplasia and gastric cancer

PurposeThe main scope of this study was to evaluate the importance of selected DNA variants for developing inflammation of gastric mucosa and carcinogenesis in gastrointestinal diseases in patients infected with Helicobacter pylori. Patients and methodsPatients subjected to analysis constituted a group of 131 consecutive cases, with control groups consisting of 100 healthy volunteers and 13 dyspeptic patients. Molecular analysis included the following genes: TP53 (c.743 G > A, c.746 G > A, c.749C > T), MSH2 (c.942 + 3A > T), MLH1 (c.2041 G > A), NOD2/CARD15 (c.3016_3017insC, c.802C > T), IL1A (c.-949C > T) and IL1B (c.315C > T). DNA variants were detected using PCR-RFLP, pyrosequencing and sequencing. ResultsMutations of the analyzed genes were observed more frequently in patients with a higher degree of mucosal lesions (50.9%) than in patients with milder mucosal changes (27.6%). Single mutations and polymorphisms did not affect the course of the disease. Our analysis confirms the influence of the NOD2/CARD15 c.802C > T polymorphism on the development of mucosal changes. A correlation of the frequency of the CT genotype of the NOD2/CARD15 c.802C > T polymorphism with the NOD2/CARD15 c.3016_3017insC mutation was observed. The TT genotype frequency in the c.315C > T IL1B gene polymorphism was statistically significantly higher in patients with mucosa changes. ConclusionsAccumulation of molecular abnormalities may increase the susceptibility to inflammatory response of the gastric mucosa in H. pylori-infected patients and play an important role in the development of chronic active gastritis, atrophy, intestinal metaplasia, dysplasia and the intestinal type of gastric cancer. The severity of gastric mucosal damage correlates with the presence of mutations in the gastric mucosa and the age of patients.

PD-1 Polymorphisms Are Associated with Susceptibility of Acute Anterior Uveitis in Chinese Population.

Acute anterior uveitis (AAU) is an ordinary type of uveitis, which is an autoimmune disease produced by T cells. Programmed apoptosis protein 1 (PD-1) is a vital negative regulatory protein of immune tolerance. We detect the single nucleotide polymorphisms (SNPs) rs41386349, rs10204525, and rs2227982 of PD-1 to investigate the correlation between PD-1 polymorphisms and AAU. A total of 166 AAU patients and 263 controls were recruited in this case-control study. Compared with controls, the frequencies of the GG genotypes were higher in rs10204525 in AAU patients (p = 0.012). There were obvious increases in frequencies of the TT genotypes in rs2227982 and the GG genotypes in rs10204525 in human leukocyte antigen (HLA)-B27-negative AAU patients compared with controls (p = 0.03; p = 0.015, respectively). There were also increases in frequencies of TT genotypes in rs2227982 and the GG genotypes in rs10204525 in the patients without ankylosing spondylitis (AS) when compared with controls (p = 0.021; p = 0.003, respectively). Furthermore, the frequencies of TT genotypes in rs2227982 were higher in female patients diagnosed with AAU than with control group (p = 0.033). Our results showed that SNPs rs2227982 and rs10204525 were interrelated to AAU; the influence on AAU could be related with gender, HLA-B27, and AS status.

Initial determination of the association between SNP rs3937033 on the D-LOOP mtDNA and breast cancer in Vietnam

Breast cancer (BC) is the most common cancer among women and accounts for the highest mortality rates in the developing countries, including Vietnam. D-loop, is a non-coding region in mitochondrialcircular DNA molecules, related to control the replication and transcription of mitochondrial genes. D-loop mutations cause the dysfunction of the respiratory chain, which contributes to the process of BC. SNP rs3937033 (T/C) on D-loop was reported to have the association with BC in Europe America population (OR [95%CI]= 1.98 [1.25–3.12], P=0.036), and Caucasian (OR[95%CI]= 21 [2.15–204.6], P=0.003). In this study, the High Resolution Melting (HRM) method is optimized for genotyping 100/100 cases/controls samples, then to determine the association between the disease and this SNP. TT, TC and CC genotype frequencies in patient group (36 %, 3 % and 61 %) and control group (23 %, 1 % and 76 %) were calculated based on the results of genotyping by optimal HRM method with the annealing temperature is 66 0C. Association analysis result showed that T allele increases the risk of breast cancer patients up to 1.41 times (OR [95% CI] = 1.41 [1.3-1.92], Pallele = 0.03). Therefore, SNP rs3937033 could be a potential biomarker for early BC diagnosis in Vietnamese. However, this research needs to be conducted with a larger sample size to reach the greater confidence.

Genetic polymorphisms of methylenetetrahydrofolate reductase C677T and risk of ischemic stroke in a southern Chinese Hakka population.

Previous studies have shown that methylenetetrahydrofolate reductase (MTHFR) gene to be a genetic risk factor for the susceptibility to ischemic stroke. The aim of this case-control study was to investigate whether the polymorphisms of MTHFR C677T were associated with the susceptibility to ischemic stroke in a southern Chinese Hakka population. In this study, a total of 1967 ischemic stroke patients and 2565 controls of Chinese Hakka ethnicity were recruited. The MTHFR C677T polymorphisms were genotyped by polymerase chain reaction (PCR) amplification and microarray method. The risk of ischemic stroke was estimated by logistic regression analysis. The frequencies of CC, CT, and TT genotypes were 52.67% versus 55.63%, 40.31% versus 38.52%, and 7.02% versus 5.85% in patients with ischemic stroke versus controls, respectively. The frequency of T allele was significantly higher in ischemic stroke patients (27.17%) than in controls (25.11%) (P = .026, odds ratio [OR] 1.113, 95% confidence interval [CI] 1.013–1.223). The homozygous TT genotype in the ischemic stroke patients was associated with increased risk (P = .049, OR 1.132, 95% CI 1.001–1.281) when compared with the controls after adjustment for age and sex. The positive association was only found in dominant model without adjustment for age and sex (P = .047, OR 1.127, 95% CI 1.002–1.268). Also, the carrier status of the MTHFR T allele was identified as an independent risk factor for the development ischemic stroke even after the adjustment for conventional risk factors (P = 0.047, OR 1.109, 95% CI 0.964–1.225). Our results provide evidence that variants of MTHFR C677T gene may influence the risk of developing ischemic stroke in a southern Chinese Hakka population. Further studies are needed to confirm this association, which will promote the development of strategies for prevention and treatment of ischemic stroke in our study population.

Relationship Between Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms with Obesity and Metabolic Syndrome in Ethnic Mongolians.

BackgroundThe distribution of fat mass and obesity-associated gene (FTO) genes rs9939609 and rs1421085 in obese and normal ethnic Mongolians was analyzed to investigate the association of FTO gene polymorphisms with obesity and metabolic syndrome in ethnic Mongolians.Material/MethodsThe genotypes of FTO genes rs9939609 and rs1421085 in 500 subjects were detected by allele-specific PCR (AS-PCR). General characteristics and clinical biochemical indicators were compared between the obesity group and the control group. The correlation between different genotypes and obesity metabolic index was also analyzed.ResultsBody mass, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), SBP, DBP, FPG, triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were higher, while HDL-C was lower in the obesity group compared with controls. The frequencies of TT genotype and T allele in the obesity group were higher than those in the control group. The frequencies of these 3 genotypes and allele frequencies of Rs1421085 were comparable between the 2 groups (P>0.05). The risk of obesity in Mongolian individuals carrying rs9939609 AT genotype was 1.312 times higher and the risk in those carrying AA genotype was 1.896 times higher than in individuals with TT genotype. The body weight, BMI, WC, HC, and WHR in individuals with rs9939609 AA and AT genotypes were significantly higher than in those with TT genotype.ConclusionsThe AT/AA genotype and allele A of rs9939609 are associated with an increased risk of obesity.

Interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism is not associated with diabetic nephropathy (DN) in Caucasians with type 2 diabetes mellitus (T2DM).

Diabetic nephropathy (DN) is a microvascular complication that affects up to 40% of diabetic patients and can lead to end-stage kidney disease. Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, IL-18 and tumor necrosis factor-α (TNFα) have been linked to the development and progression of DN. The aim of our study was to examine the relationship between interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism and DN in patients with type 2 diabetes mellitus (T2DM). This study is a continuation of our previous research on the association between angiotensinogen (AGT) gene polymorphisms and DN in patients with T2DM. We included 651 unrelated Slovenian (Caucasian) patients who had had T2DM for at least 10 years. The participants were classified into a group of T2DM patients with DN (276 cases) and a group without DN (375 controls). IL4 rs2243250 polymorphism was analyzed using a TaqMan SNP genotyping assay and StepOne Real-Time PCR System. The frequencies of rs2243250 TT, CT and CC (wild type) genotypes were 3.2%, 29.4% and 67.4%, respectively in patients with DN, and 2.7%, 34.4% and 62.9%, respectively in controls. Our logistic regression analysis adjusted for gender, age, diabetes duration, and glycated hemoglobin showed no association between rs2243250 and the risk for DN (OR 1.06; CI 0.37-3.05; p = 0.9). IL4 rs2243250 is not associated with DN in our subset of Slovenian patients with T2DM.

Genetic Variation in Intergenic and Exonic miRNA Sequence and Risk of Multiple Sclerosis in the Isfahan Patients

MicroRNAs (miRNAs), have been documented to perform a key role in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory and autoimmune disease. Recent studies have shown that single nucleotide polymorphism in the sequence of the miRNA may change their production and expression which can lead to miRNA dysfunction and pathogenicity. Some studies have reported the relationship between miRNA polymorphism and the increased risk of autoimmune disease. This study was conducted to investigate the association between mir155 rs767649, mir196a2 rs11614913 and mir23a rs3745453 polymorphism and the risk of multiple sclerosis in the Iranian MS patients in Isfahan. A population of 80 patients and the same number control were selected. After DNA extraction, genotyping was performed through tetra amplification refractory mutation system-PCR method (T ARMS PCR). The frequencies of TT, TC and CC genotypes of mir23a were 46, 35 and 20% in MS patients and 42, 14 and 24 in healthy subjects respectively. These results showed that individuals carrying the genotypes of rs3745453 TC had a 2.3-fold increased risk of MS (OR=2.3, p=0.048). There was no significant difference between genotypes and allele frequency of mir155 and mir196a2 in patients and healthy controls (p>0.05). Our findings specified that CT heterozygosity in mir23a gene significantly related with risk of MS. Unlike mir155 and mir196a2, mir23a rs3745453 may have contributed to the etiology of MS in Isfahan patients. However, extensive studies are required to gain more reliable and authentic results.

XRCC1 rs1799782 (C194T) polymorphism correlated with tumor metastasis and molecular subtypes in breast cancer.

BackgroundBreast cancer, a malignant tumor with its highest incidence in women, affects physical and mental health, and can even be life-threatening. In recent years, its incidence has continued to grow, accompanied by a trend of younger onset. XRCC1 is well known as a DNA-repair gene, and its abnormal expression is related to the occurrence of various malignant tumors.MethodsIn this study, we detected XRCC1 expression and investigated its association with the XRCC1 rs1799782 polymorphism. XRCC1 was overexpressed to investigate its effect on in breast cancer cells. CCK8 and clone formation efficiency assay were used to detect cell proliferation. Transwell assay was performed to confirm cell migration and invasion. Flow cytometry was used to detect cell apoptosis.ResultsIn 118 breast cancer samples, CC genotype frequency was 49.15% (58 of 118), CT genotype frequency was 42.37% (50 of 118), and TT genotype frequency was 8.48% (ten of 118). Lymphatic metastasis was associated with a higher frequency of XRCC1 rs1799782 polymorphism (P<0.05), and breast cancer patients with positive PR, HER2, and negative ER had high XRCC1 rs1799782 frequency (P<0.05). Meanwhile, XRCC1 had low expression in breast cancer (74.6%, 88 of 118) and high expression in ER-negative, PR-negative, HER2-positive and Ki67-low-expression patients. XRCC1 rs1799782 may play an important role in the development and metastasis of breast cancer. These results differ from previous studies that did not suggest that rs1799782 is effective in breast cancer. We also investigated the role of XRCC1 in breast cancer progression.ConclusionWe have proved that XRCC1 can inhibit proliferation and invasion and promote apoptosis of breast cancer cells. XRCC1 expression was regulated by the JNK pathway. We found that the JNK inhibitor SP600125 significantly inhibited the growth of breast cancer cells, and consider it a potential drug for breast cancer.

Relationship between genetic polymorphism of MTHFR C677T and lower extremities deep venous thrombosis

ABSTRACTObjective: To investigate the association between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and the formation of lower extremities deep venous thrombosis, and to evaluate the etiology of deep venous thrombosis.Methods: Polymorphisms of the 677th site C/T in MTHFR gene for 101 patients with lower extremities deep venous thrombosis (DVT group) and 120 healthy subjects (control group) were detected by polymerase chain reaction with sequence-specific primers. Genotype and allelic frequencies were compared between the two groups.Results: Genotype frequencies of CC, CT and TT in MTHFR C677 T were 41.58, 25.74 and 32.67% in DVT group, and 58.33, 23.33 and 18.33% in control group, respectively. There was a significant difference in TT genotype frequency between the two groups (P <0.05).Conclusion: The frequency of MTHFR 677TT genotype may be correlated with the morbility of DVT.