Homozygous CC Genotype Research Articles

Role of SREBP2 gene polymorphism on knee osteoarthritis in the South Indian Hyderabad Population: A hospital based study with G595C variant

IntroductionOsteoarthritis (OA) is a multifactorial disease with genetic factors playing a crucial role, and it has been associated with a family history of obesity. G595C polymorphism in the sterol regulatory element-binding protein 2 (SREBP2) gene has demonstrated an association with knee osteoarthritis (KOA) patients. However, this polymorphism has been never explored in an Indian population. Hence, the current study aimed to examine whether G595C (rs2228314) polymorphism in SREBP2 gene was associated with KOA susceptibility in the South Indian Hyderabad population. MethodsG595C polymorphism was genotyped with 200 KOA cases and 200 healthy controls using polymerase chain reaction-restriction fragment length polymorphism analysis. ResultsA significant association was observed between age, body mass index (BMI), and family histories in KOA cases and controls (p < 0.05). The current allele (C vs G; OR-2.8 [95%CI = 2.1–3.7]; p < 0.0001) and genotype analysis confirms the significant association with (GC + CC vs GG; OR-3.5 [95%CI = 2.3–5.3]; p < 0.0001 & GC vs GG + CC; OR-1.7 [95%CI = 1.0–2.9]; p = 0.02) KOA vs. control subjects. On stratification analysis, genotype CC and C allele were associated with KOA. Gender association failed to demonstrate positive genotype frequencies (p > 0.05). Multifactor-dimensionality reduction (MDR) analysis showed a positive association with BMI and G595C genotypes (p < 0.05); 51% of the homozygous variant CC genotypes were present in obesity subjects. ConclusionIn conclusion, our findings suggest that G595C polymorphism in SREBP2 gene is associated with KOA in the South Indian Hyderabad population and presents scope for further investigation of the gene's function in KOA.

Association of the Vascular Endothelial Growth Factor Gene Polymorphism +936 C/T with Diabetic Neuropathy in Patients with Type 2 Diabetes Mellitus

Peripheral neuropathy is one of the most common late complications of diabetes. Vascular endothelial growth factor (VEGF) gene polymorphisms have been associated with the development of peripheral neuropathy in different populations of patients with type 2 diabetes mellitus (DM2). To analyze the prevalence of the +936C/T VEGF gene polymorphism among patients with DM2 with and without peripheral neuropathy. 218 unrelated DM2 patients, 90 with and 128 without peripheral neuropathy were genotyped for the +936C/T VEGF gene polymorphism using PCR amplification followed by restriction length polymorphism analysis. The CC homozygous VEGF+936C/T (rs3025039) was the predominant genotype in DM2 patients with peripheral neuropathy, whereas the predominant genotype in patients without neuropathy was the heterozygous C/T. No statistical association was found between genotype distribution and the presence of neuropathy (p=0.063). The distribution of the genotypes according to the dominant (CC vs. CT+TT) and recessive (TT vs. CT+CC) models showed that the homozygous CC and TT genotypes, respectively, are not risk factors for neuropathy. The CT genotype conferred a protective effect as seen in the over-dominant model (CT vs. CC+TT) (OR=0.52; 95% CI=0.300-0.90; p=0.019). We conclude that the VEGF+936C/T (rs3025039) gene polymorphisms are related to peripheral neuropathy in Mexican DM2 patients, with the heterozygous genotype potentially conferring a protective effect.

Clinical significance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in western Chinese tuberculosis patients

ObjectivesTuberculosis (TB) remains a global public health problem. Recent studies have implicated long non-coding RNAs and their variants as possibly playing important roles in TB. The aim of this study was to assess the clinical relevance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in a western Chinese population. MethodsThis case–control study included 467 TB patients and 473 healthy controls from West China Hospital. The expression levels of lnc-AC145676.2.1-6 and lnc-TGS1-1 were analyzed by reverse transcriptase quantitative real-time PCR. Single-nucleotide polymorphism genotyping was performed using a custom-designed 2 × 48-Plex SNPscan kit. ResultsIt was observed that lnc-AC145676.2.1-6 and lnc-TGS1-1 expression levels were both obviously down-regulated in TB patients. In addition, a lower expression level of lnc-TGS1-1 was associated with the presence of thrombocytopenia in TB patients during anti-TB treatment, and the homozygous CC genotype of rs4737420 correlated with a decreased risk of leukopenia, compared with individuals with the T allele (TT/CT genotype), in the dominant mode. ConclusionsFor the first time, potential TB-associated promoting effects were identified for the decreased expression levels of lnc-AC145676.2.1-6 and lnc-TGS-1, while lnc-TGS1-1 and its variant rs4737420 may be predictive indicators of anti-TB drug-induced adverse drug reactions. Larger validation studies on different populations are warranted to confirm these findings.

Асоціація поліморфізму гена ендотеліальної NO-синтази (NOS3–786T&gt;C) з тяжкістю діастолічної дисфункції лівого шлуночка і легеневої гіпертензії в пацієнтів із серцевою недостатністю та збереженою фракцією викиду лівого шлуночка

The aim – to determine polymorphisms of the nitric oxide synthase gene -786T&gt;C rs 2070744 and the association of the corresponding genotypes with the severity of left ventricle (LV) diastolic dysfunction (DD), pulmonary hypertension (PH) and elastic properties of the arteries in patients with arterial hypertension (AH) and heart failure (HF) with preserved ejection fraction (EF).Materials and methods. We included 69 patients (pts) with AH and HF with preserved EF (31 female (41.9 %) and 33 male (58.1 %)), aged 67.4±10.2 years; II–III class NYHA, hemodynamically stable. According to Shah’s criteria, the «aging» phenotype was identified in 11 (15.9 %) pts, «obesity» – 14 (20.3 %) pts, «coronary artery disease» – 16 (23.2 %) pts, «pulmonary hypertension» – 17 (24.6 %) pts (with a significant predominance of patients with CC genotype), «arterial hypertension» – 17 (24.6 %) pts.Results and discussion. «Wild» homozygous TT genotype was found in 34 pts (49.3 %, TT group), heterozygous TC genotype – in 21 pts (30.4 %, TC group) and «mutant» homozygous CC genotype – in 14 pts (20.3 %, CC group). The groups did not differ in gender (male 19 or 55.9 %, 12 or 60 % and 11 or 61.1 %, p&lt;0.05) and average age (67.1±8.9, 65.4±10.6 and 64.9±10.3 years p&gt;0.05), and in prevalence of comorbidities. The worst result of 6-minute walk test was in the CC group compared with TT and TC (371.8±77.7, 385.7±85.4 and 314.3±69.1, p&lt;0.05), as well as higher NT-proBNP level (668.1±317.8, 636.9±433.2 and 806.9±369.7, p&lt;0.05), greater LVMI (187.4±37.1, 182.2±25.7 and 195.2±28.5, p&lt;0.05). There was markedly more pronounced DD LV in the CC group compared with TT and TC, according to average e’ (p&lt;0.05) and E/e’ (p&lt;0.05). SPAP was the highest in the CC group (p&lt;0.05), as well as PCWP and TPG (p&lt;0.05). Patients of the CC group had worse elastic properties of arteries according to AIx75 (p&lt;0.001) and PWVc-f (p&lt;0.05), with a decrease in SAC (by 38.2 and 29 % compared to TT and TC (p&lt;0.05) and an increase in Ea, respectively, by 21 and 9 % (p&lt;0.05). According to the cuff test in patients of the CC group, compared with those in the TT and TC groups, worsening of endotelium-dependent vasodilation, respectively by 19.8 and 17.3 % (p&lt;0.05) was revealed.Conclusions. Compared to other polymorphisms, the CC genotype of the NOS3 rs 2070744 gene is associated with greater severity of DD LV, LH and impaired LV diastolic function and elastic properties of systemic arteries, according to pulse wave analysis in patients with AH and HF with preserved EF.

Clinical Importance of Estrogen Receptor 1 (ESR1) Gene Polymorphisms and Their Expression Patterns in Coronary Artery Disease Patients: A Study from India.

The influence of Estrogen Receptor 1 (ESR1) gene -397T>C (PvuII) and -351A>G (XbaI) polymorphisms on the risk of development of coronary artery disease (CAD) in the north Indian population was analysed. We hypothesized that ESR1 gene polymorphisms may influence the susceptibility to CAD through variation in Estrogen Receptor α (ERα) expression. To assess this concept, we evaluated ERα mRNA expression in blood plasma of CAD patients. The study included hundred CAD patients who showed presence of greater than 50% luminal stenosis in at least one major coronary artery in angiography along with hundred age and sex matched healthy controls. The ESR1 polymorphisms were investigated by PCR-RFLP. Quantitative Real Time PCR was carried out for the measurement of ERα mRNA expression. The results showed that genotypic frequencies of ESR1 -397T>C and -351A>G gene polymorphisms were significantly higher in CAD patients than control subjects (p < 0.0001). A significantly increased CAD risk was also found in dominant and codominant inheritance model for both of the SNPs. In gender based analysis these findings were replicated only in male subgroup. In case of -397T>C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2-∆ct = 0.28). A mutant 'C' allele, dose dependent, significant decrease in trend in ERα mRNA expression was observed, with lowest expression in mutant homozygous CC genotype (2-∆ct = 0.09), and intermediate expression level in heterozygous TC genotype (2-∆ct = 0.14) subgroups of CAD patients. In conclusion, this study demonstrates a significantly heightened risk of CAD associated with the inheritance of mutant genotypes of ESR1 -397T>C and -351A>G gene polymorphisms, in the north Indian population. This is the first report of a lowered ERα mRNA expression in conjunction with the presence of mutant 'C' allele of ESR1 -397T>C polymorphism with consequent increased CAD susceptibility.

Association of genetic polymorphisms of miR-145 gene with telomere length in omethoate-exposed workers

Omethoate, an organophosphorous pesticide, causes a variety of health effects, especially the damage of chromosome DNA. The aim of the study was to assess the correlation between polymorphisms of encoding miRNA genes and telomere length in omethoate–exposure workers. 180 workers with more than 8 years omethoate–exposure and 115 healthy controls were recruited in the study. Genotyping for the selected single nucleotide polymorphisms loci were performed using the flight mass spectrometry. Real-time fluorescent quantitative polymerase chain reaction(PCR) method was applied to determine the relative telomere length(RTL) in human peripheral blood leukocytes DNA. After adjusting the covariate of affecting RTL, covariance analysis showed that the female was significantly longer than that of the male in control group(P < 0.046). For the miR-145 rs353291 locus, this study showed that RTL of mutation homozygous AG+GG individuals was longer than that of wild homozygous AA in the exposure group (P = 0.039). In the control group, RTL with wild homozygous TT genotype in miR-30a rs2222722 polymorphism locus was longer than that of the mutation homozygous CC genotype (P = 0.038). After multiple linear regression analysis, the independent variables of entering into the model were omethoate–exposure (b = 0.562, P < 0.001), miR-145 rs353291 (AG+GG) (b = 0.205, P = 0.010). The prolongation of relative telomere length in omethoate exposed workers was associated with AG+GG genotypes in rs353291 polymorphism of encoding miR-145 gene.

Genotyping of vitamin D receptor FOKI polymorphism as a predictor for type 2 diabetes mellitus by a tetra primer-ARMS-PCR assay

The article describes diabetes mellitus which is a chronic disease resulting from a complex inheritance-environment interaction. Vitamin D has a role in the type 2 diabetes mellitus (T2DM) pathogenesis through the relationship between the deficiency of vitamin D and resistance of insulin. The main objective of the article is to analyze the correlation of the receptor's vitamin D FOKI gene polymorphism with T2DM in a sample of the Iraqi population. One-hundred-ninety-five Iraqi individuals (94 T2DM and 101 controls) were enrolled in this case-control study. FOKI SNP of the VDR gene was genotyped by using Tetra primer ARMS-PCR. The homozygous genotype CC and the allele C were correlated with significant risk of T2DM (OR=2.7, 95% CI; 1.5–4.8, p=0.0009) and (OR= 1.8, 95% CI; 1.17–2.9, p=0.006) respectively. FOKI polymorphism has causative effects on the risk for T2DM and Tetra-primer ARMS-PCR method was simple, economic and could be useful to genotype VDR gene polymorphisms in routine clinical and resource-limited settings.

Genetic polymorphism of miRNA-196a and its target gene annexin-A1 expression based on ethnicity in Pakistani female breast cancer patients.

Objective:To evaluate the association of miR-196a rs11614913 C/T genetic variation and its target gene annexin A1 mRNA expression with breast cancer risk in Pakistani female ethnicities.Methods:This case control study, conducted from March 2017 to November 2018 included 295 breast cancer patients, 295 controls of three Pakistani ethnicities and archived 100 samples of cohort group for genotyping and expression profiling. Genotyping of miR-196a (rs11614913 C/T) was done by ARMS PCR technique. Annexin-A1 (ANXA1) mRNA expression was measured with qRT-PCR and detection of protein expression of ANXA1 was done by immunohistochemistry.Results:CC homozygous genotype of miR-196a rs11614913 was present in 81.4% of cases and 73.9% controls. C/T polymorphism was found to be significantly associated with decrease risk of breast cancer (OR=0.25 (0.11- 0.58, p <0.05). Similar trend was seen with the minor T allele (OR=0.55 (0.39-0.77, p <0.05, and both dominant and recessive models (OR=0.64; p=0.02 and OR=0.26, p=0.00). In the KPK ethnic group significant decrease association with breast cancer risk was observed (OR= 0.22 (0.09-0.53, p < 0.05). Immunohistochemical staining showed loss of ANXA1 protein expression in 72 samples, and significant association was observed with pathological type p=0. 00 and triple negative receptor status p=0.03 and with genotypes of miR-196a p=0.00. Increase relative expression of 2.81± .88 by qPCR analysis of ANXA1 mRNA was noted with TT genotype.Conclusions:Our results demonstrate that miR-196a rs11614913 C/T polymorphism is associated with a decreased risk and loss of protein expression in breast cancer in the Pakistani population.

Single nucleotide polymorphism analysis in meat-production related genes in broiler chickens

In broiler chickens, the intensive selection for growth rate, feed efficiency, body composition (breast muscle weight) traits in the last decades was successful. To improve economically important characteristics, it is possible to use molecular markers associated with meat production traits. The aim of this study was to examine genotype polymorphisms in ROSS 308 broilers for thyroid hormone responsive Spot14α, insulinlike growth factor 1 (IGF1), IGF-binding protein 2 (IGFBP2), somatostatin (SST) and prolactin (PRL) genes. A further goal of this investigation was to study the relationship between the polymorphisms and phenotypic characteristics.&#x0D; In the investigated broiler population, the frequency for CC homozygous genotype was 0.77 in Spot14α (AY568628), AA homozygous genotype was 0.80 in IGF1 (M74176), GG homozygous genotype was 0.85 in IGFBP2 (U15086), DD homozygous genotype was 0.60 in PRL (FJ663023 or FJ434669). Only the AA homozygous genotype was found in SST (X60191). Chickens with AC genotype in Spot14α, and with GG genotype in IGFBP2 had higher body weight (BW) and carcass weight (CW), compared to CC and GT genotypes. However, the differences were not significant (P&gt;0.05). There was significant association (P&lt;0.05) between PRL genotypes and body and carcass weight, where chicken with homozygous DD surpassed individuals with homozygous II genotypes.

Association of SNPs in the Promoter Regions of VEGF (rs699947 и rs2010963), ICAM1 (rs281437) and ET-1 (rs1800541) with Serum Levels of Related Proteins and Alcoholic Liver Cirrhosis Risk

Background: Uncontrolled use of alcohol can lead to the development of cirrhosis of the liver, which is manifested by fibrosis with the formation of regenerative nodes, an increase in pressure in the portal vein system and impaired liver function. Hepatic endothelium dysfunction during the formation of portal hypertension is accompanied by an increase in the level of protein molecules involved in the functioning of the endothelium: vascular endothelial growth factor A (VEGF-A), a soluble form of the intercellular adhesion molecule (s-ICAM-1) and endothelin-1 (ET -one). It is assumed that elevated levels of VEGF-A, s-ICAM-1 and ET-1 in alcoholic liver cirrhosis (AHC) may be interconnected with the structure of polymorphic loci, the promoter regions of the respective genes, which in turn may be a genetic risk factor for developing cirrhosis.Aims: Investigate the relationship of carriage of variant forms of polymorphic loci located in the promoter regions of VEGF-A, ICAM-1 and ET-1 with the level of the corresponding proteins in the blood serum and the risk of AHC.Materials and methods: The main group consisted of patients with pathological dependence on alcohol, aggravated by cirrhosis of the liver (AHC, n=60). The control group consisted of persons suffering from alcohol abuse, without liver pathology (AA, n=24). The observation period was the period of hospitalization. The serum levels of VEGF-A, s-ICAM-1 and ET-1 were evaluated by enzyme immunoassay. The distribution of variant forms of polymorphic loci located in the promoter regions of the VEGF-A genes (rs699947 and rs2010963), ICAM1 (rs281437) and ET-1 (rs1800541) in the studied sample was performed by real-time PCR.Results: The development of alcoholic cirrhosis was accompanied by a significant increase in the concentration of VEGF-A, s-ICAM-1 and ET-1 in serum. At the same time, direct correlations between the concentrations of VEGF-A, s-ICAM-1 and ET-1 in serum and the diameter of the portal vein in persons with liver cirrhosis were revealed. Patients with AHC are often carriers of the G allele of rs1800541 locus, located in the promoter of the ET-1 gene, compared with individuals suffering from control without liver pathology, which is associated with an increased risk of developing cirrhosis in alcohol dependence. The carriage of the C allele rs699947, as well as the C allele rs2010963 located in the promoter of the VEGF gene was associated with an increased level of VEGF-A in the AHC compared to carriers of this allele in the AA group. In addition, in the group of patients with AHC, carriers of allele C, homozygous CC genotype and heterozygous GC genotype of rs2010963 locus compared with carriers of G allele or homozygous GG genotype, respectively, were characterized by elevated serum VEGF-A levels.Conclusion: Carrier allele G of the rs1800541 locus (ET-1) is a risk factor for liver cirrhosis with alcohol abuse. The carriage of the C allele rs699947, as well as the C allele rs2010963 located in the promoter of the VEGF gene, can determine the elevated serum VEGF-A level in the AHC.

Polymorphism of Vitamin D Receptor (re2228570) in Sera of Coronary Artery Diseases and its Association with Various Anthropometric and Biochemical Parameters

Objective : Coronary artery disease is increasing and accounts for a high proportion among others diseases. In Iraq various studies have been reported that the polymorphism of vitamin D receptor VDR-Fok I gene like rs 2228570 are associated with CAD patients.&#x0D; Aim: This study was aimed to investi­gate the association between the SNP of VDR Fok I (rs2228570) gene with various anthropometric and biochemical parameters as a risk for CAD in Iraqi population.&#x0D; Methods and Materials : The current case - control study consisted of 300 samples , 150 of them were obtained from CAD patients who underwent the angiography department – heart centre – Al-Hussein Teaching Hospital, Al-Hussein Medical City / Holy Kerbala - Iraq and another 150 healthy control samples. Phenotypic data included body mass index (BMI), levels of fasting blood sugar (FBS), lipid profile, and blood urea, serum creatinine. Genotyping of rs2228570 polymorphism was carried out by PCR–RFLP method. DNA was extracted from genomic whole blood and genotyping was achieved with specific primers to amplify fragments for digestion with restriction enzymes. The enzyme Fok I was used for the digestion of VDR gene product followed by electrophoresis on agarose gel. Various statistical analyses were applied to analyse the data.&#x0D; Result: Digestion of VDR – Fok I gene product (PCR-product ) exhibited an amplicon size of 273 bp, when this amplicon digested with Fok I enzyme, it gives three genotypes indicated one (273bp), two (75 bp + 198 bp) and three (75 bp + 198 bp + 273 bp ) bands for those with wild type (TT), homozygous (CC) and heterozygous (TC) genotypes respectively. Genotype frequencies of rs2228570 polymorphism were found to be consistent with Hardy–Weinberg equilibrium with allele frequencies of TT wild genotype (33.3%), TC heterozygous genotype (46.7%), and CC homozygous genotype (20%) in cases of CAD group while 66.7%, 30 % and 3.3 % for wild, heterozygous, and homozygous in the control group respectively. The homozygous genotype (CC) was significantly (OR= 7.25, CI 2.74-19.20 , P&lt;0.001 ) increased the risk of CAD seven and quarter folds with respect to those of the wild type (TT) after adjustment for age, sex and BMI, while the TC genotype significantly (OR = 2.04, CI 95% ; 1.27-3.28 , P&lt;0.001) raised the risk of CAD by two folds. Co-dominant genotypes of rs2228570 polymorphism exhibited significant association with anthropometric and biochemical parameters such as BMI, and lipid profile among patients groups as compared with control groups.&#x0D; Conclusion: The obtained results improved that the gene polymorphism of VDR-Fok I was associated with high risk for development and progression of CAD and exhibited a significant association with increased BMI and lipid profile of coronary artery diseases of Iraqi population.

The genetic variants of solute carrier family 11 member 2 gene and risk of developing type-2 diabetes

Type-2 diabetes (T2DM) is a metabolic disorder characterized by long-terminsulin resistance, impaired insulin secretion from β-cells, and loss of beta cell mass and function. Inflammation and oxidative stress play a key role in the development of diabetes and are associated with insulin resistance. Notably, recent studies have demonstrated an association between body iron stores, insulin resistance and T2DM. Free iron, a powerful pro-oxidant molecule, is involved in oxidative stress, lipid peroxidation and endothelial dysfunction via its ability to generate free radicals. Specifically, the accumulation of iron in beta cells triggers oxidative stress and DNA damage, which have been reported to be associated with β-cell death and apoptosis. Solute carrier family-11 member-2 (SLC11A2) functions to transport ferrous iron and some divalent metal ions throughout the plasmamembrane and across endosomalmembranes. Functional polymorphisms in the SLC11A2 gene have been reported to cause excess storage of iron, resulting in iron overload. In this study, we evaluated the association between T2DM and SLC11A2 gene variants IVS4+44C/A, 1303C/A and 1254T/C by performing PCR-RFLP analysis on 100 T2DM patients and 100 healthy subjects. PCR products were digested with MnlI, MboI and SfanI restriction endonucleases and the products were then separated by 3% agarose gel electrophoresis. The genotype frequencies of the 1254T/C and 1303C/A SLC11A2 gene variants did not differ between healthy controls and T2DM patients (P > 0.05). But, inrecessive model (P = 0.037) and homozygous CC genotype (P = 0.030) for IVS4+44C/A showed significant correlation with T2DM risk. It is thought that presence of C allele of IVS4+44C/A plays pathological roles.

SNPs in 3′-UTR region of MBL2 increases susceptibility to recurrent vulvovaginal infections by altering sMBL levels

Recurrent vulvovaginal infections (RVVI), owing to their adverse health consequences, have become a serious dilemma worldwide. Low serum levels of Mannose-Binding Lectin (sMBL), a main component of innate immunity, was found to be associated with RVVI risk, though complete genetic bases are still elusive. To reveal unrecognised regulatory variants, 3′-UTR region of MBL2 with six putative functional SNPs i.e. rs10824792, rs2120132, rs2120131, rs2165813, rs2099903 and rs2099902 was sequenced and genotyped in the present study for 109 RVVI cases and age matched healthy controls. sMBL levels were measured by enzyme-linked immunosorbent assay. The homozygous CC genotype of rs10824792 polymorphism was found to be conferring risk (OR = 2.94) of developing RVVI. Significantly high frequency of corresponding CC genotype was found in Vulvovaginal Candidiasis (VVC) and Mixed Infections (MI) relative to controls. Significantly insufficient sMBL levels were observed in RVVI and its types (Bacterial Vaginosis, VVC and MI) than controls. sMBL levels varied for rs10824792 SNP as expected from the genetic analyses. Six marker haplotype analyses have shown CTTGCT, the haplotype containing only risk allele of rs10824792, conferred risk of RVVI and its types by lowering sMBL levels. In conclusion, a 3′-UTR SNP i.e. rs10824792 was identified as novel associated genetic marker for contributing low sMBL levels and RVVI risk. Our findings contribute to the novel future research directions for the development of emerging MBL substitution as effectual therapy for RVVI.

Influence of -174G/C IL-6 gene polymorphism on the susceptibility to rheumatoid arthritis in children and adults in the Republic Of Belarus

The usage of clinical and instrumental methods only may be not sufficient for early diagnosis of autoimmune rheumatic diseases, as well as for their course prediction. The progress of modern rheumatology is largely conditioned by the investigation of molecular-genetic nature of diseases and the identification of biomarkers that can significantly improve diagnostics and therapeutic approach. The present study aimed to evaluate the effect of -174G/C IL-6 gene polymorphism on the risk of developing rheumatoid arthritis (RA) in children and adults in Republic of Belarus. It was established that the CC genotype frequency (p = 0.01, OR = 2.19; 95 % CI [1.31-3.67]) as well as the С allele frequency (p = 0.03; OR = 1.44; 95 % CI [1.04-2.00]) was significantly higher among patients with juvenile idiopathic arthritis (JIA) in the entire group and especially in girls (p = 0.04, OR = 2.55; 95 % CI [1.22-5.36]) in comparison with the controls. In addition, there is a tendency to higher frequency of the С allele in adult patients with RA (p = 0.07), reaching statistical significance in the case of RF-negative arthritis (p = 0.03, OR = 3.04; 95 % CI [1.15-8.06]). The minor С allele (p = 0.03, OR = 2.04; 95 % CI [1.09-3.82]) and homozygous CC genotype (p = 0.02, OR = 3.34; 95 % CI [1.38-8.07]) are also associated with seronegative polyarthritis in children. Thus, the presence of this allele in the tested locus increases the likelihood of developing certain rheumatoid arthritis subtypes in adults and children and can be used to reveal individuals with genetic predisposition.

The association of CD40 polymorphism (rs1883832C/T) and soluble CD40 with the risk of systemic lupus erythematosus among Egyptian patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Considerable evidence supports a genetic basis for susceptibility to SLE. Genetic and functional data suggested the CD40 receptor (CD40) and CD40 ligand (CD40L) as strong candidate genes for SLE. To investigate whether CD40 gene rs1883832 C/T single-nucleotide polymorphism (SNP) and/or soluble CD40 (sCD40) are associated with SLE in the Egyptian population. The study included a hundred SLE patients, and a fifty age- and gender-matched healthy control subjects. CD40 gene rs1883832 C/T genotyping was carried out using restriction fragment length polymorphism (RFLP), while sCD40 levels were measured by ELISA. CD40 rs1883832C/T genotypes (CC, TT, and CT) as well as CD40 alleles (C and T) did not differ between SLE patients and normal control (p = 0.63, 0.37, and 0.31 respectively). Though did not reach statistical significance, carriers of genotype CT had 1.5 times more chance to develop SLE compared to wild homozygous CC genotype carriers (OR 1.44), while carriers of genotype TT had ~ 2 times more chance to have SLE than CC carries (OR 1.96). Accordingly, the carriers of the T allele had ¬1.5 times more chance to get SLE compared to the carriers of the C allele (OR 1.4). The serum sCD40 level was significantly higher in SLE patients compared to healthy control (3.4 vs. 0.8ng/mL, p < 0.001). In SLE patients, using CC as the reference genotype, serum sCD40 level was significantly higher in the carriers of the homozygous genotype TT (3.8 ± 1.3 vs. 2.9 ± 1.9, p = 0.0001), and T allele (3.6 ± 1.4 vs. 3.0 ± 1.5, p = 0.003). Moreover, sCD40 could discriminate SLE patients from normal subjects at a cutoff value of 0.885ng/mL with 98% sensitivity and 96% specificity (AUC = 0.999, p < 0.001). The study did not prove CD40 gene (rs1883832 C/T) polymorphism as a clear risk factor of SLE in this cohort of Egyptian patients, though it was highly likely associated with the carriers of T allele. In the same context, significant high sCD40 levels were observed in the T allele carriers.

MTHFR C677T gene polymorphism is not associated with preterm premature rupture of membranes in North Indian women

AimThe present study aims to understand the role of methylenetetrahydrofolate reductase (MTHFR C677T) gene polymorphism in preterm premature rupture of membranes. MethodsThe preterm premature rupture of membranes (N = 90) cases and their gestation matched controls (N = 122) were recruited from Lady Hardinge Medical College and Smt. Sucheta Kriplani Hospital. Fasting blood sample (~5 ml) was drawn and genotypic analysis of MTHFR C677T polymorphism was performed by PCR-RFLP in all the PPROM cases and controls. Fetal genotypic analysis of MTHFR C677T was performed using placental DNA in PPROM cases (N = 16) and controls (N = 23). ResultsThe genotypic frequency distribution of MTHFR C677T gene polymorphism of normal homozygous CC genotype was found to be similar among cases (76.67%) and controls (72.27%). Further, the analysis revealed a lower percentage of mutant heterozygotes (CT = 23.33%) among cases as compared to controls (CT = 27.73%). The cases and controls were not found to carry homozygous mutant TT genotype. ConclusionMTHFR C677T gene polymorphism does not seem to play a major role in association with preterm premature rupture of membranes in the North Indian women.

A7233 Polymorphism and m RNA expression of The Estrogen Receptor alpha gene in Coronary Artery Disease- A study from India

Objectives: To study the role of −397T > C ESR1 polymorphism in CAD in the north Indian population. We hypothesized that ESR1 gene polymorphism may influence the susceptibility to CAD through variation in ERα expression. In order to assess the veracity of this concept, we evaluated ERα m RNA expression in peripheral blood leucocytes of our cohort of CAD patients. Methods: 100 clinically confirmed CAD patients and normal healthy controls were included in this study. DNA and RNA from both CAD patients and healthy controls was extracted using Gene Aid DNA extraction kit and trizol RNA isolation method. We employed PCR-RFLP technique to characterize −397 T > C ESR1 gene polymorphism. Quantitative Real Time was carried out for measurement of ESR α expression on a Rotor-Gene Instrument. Results: The frequency of −397T > C ESR1 SNP of mutant homozygous (CC) plus heterozygous (TC) genotype was higher (78% vs 49%) in CAD as compared to control subjects (p < 0.0001. Moreover the ESR1 m RNA expression was highest in CAD patients with wild type homozygous TT genotype (2-Δct = 0.28) as compared to homozygous CC genotype (2-Δct = 0.09), and intermediate expression level in heterozygous TC genotypes (2-Δct = 0.14) subgroups of CAD patients. As compared to wild type TT genotype taken as reference, the fall in TC genotype (2.02 fold) and CC genotype (2.96 fold), was statistically significant (p = 0.001 and 0.008 respectively). Conclusion: Our data associates significant involvement of ESR1 polymorphism genotypes with under expression of its mRNA which consequently results in high-risk of developing CAD. However, further research is warranted on the differences of these functional polymorphisms and their impact on ESR1 gene expression and their correlation with the development of CAD.

Association Between SLC30A8 rs13266634 Polymorphism and Risk of T2DM and IGR in Chinese Population: A Systematic Review and Meta-Analysis.

Introduction: Published data regarding the association between solute carrier family 30, member 8 (SLC30A8) rs13266634 polymorphism and type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) risks in Chinese population are in-consistent. The purpose of this meta-analysis was to evaluate the association between SLC30A8 rs13266634 and T2DM/IGR in a Chinese population.Material and Methods: Three English (PubMed, Embase, and Web of Science) and three Chinese databases (Wanfang, CNKI, and CBMD database) were used for searching articles from January 2005 to January 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated with the random-effect model. Trial sequential analysis was also utilized.Results: Twenty-eight case-control studies with 25,912 cases and 26,975 controls were included for SLC30A8 and T2DM. Pooled risk allele C frequency for rs13266634 was 60.6% (95%CI: 59.2–62.0%) in the T2DM group and 54.8% (95%CI: 53.2–56.4%) in the control group which had estimated OR of 1.23 (95%CI: 1.17–1.28). Individuals who carried major homozygous CC and heterozygous CT genotype were at 1.51 and 1.23 times higher risk of T2DM, respectively, than those carrying minor homozygous TT. The most appropriate genetic analysis model was the co-dominant model based on comparison of OR1, OR2 and OR3. Five articles that involved 4,627 cases and 6,166 controls were included for SLC30A8 and IGR. However, no association was found between SLC30A8 rs13266634 and IGR (C vs. T, OR = 1.13, 95%CI: 0.98–1.30, p = 0.082). TSA revealed that the pooled sample sizes of T2DM exceeded the estimated required information size but not the IGR.Conclusion: The present meta-analysis demonstrated that SLC30A8 rs13266634 was a potential risk factor for T2DM, and more studies should be performed to confirm the association between rs13266634 polymorphism and IGR.

Polymorphisms in the H19 gene and the risk of lung Cancer among female never smokers in Shenyang, China

BackgroundLong non-coding RNA (lncRNA) H19 is a hot spot in tumor development, progression and metastasis. This study assessed the association between H19 genetic polymorphisms and the susceptibility of lung cancer.MethodsThe case-control study was conducted to evaluate the association between four selected single nucleotide polymorphisms (rs217727, rs2107425, rs2735469 and rs17658052) in H19 gene and the risk of lung cancer. There were 556 female never smoking lung cancer patients and 395 cancer-free controls. Unconditional logistic regression analysis was used to analyze the associations between four SNPs and lung cancer risks by calculating the odds ratios and their 95% confidence intervals. The gene-environment interactions were assessed on both additive and multiplicative scales.ResultsCompared with carriers carrying homozygous CC genotype, there was a statistically significant increased risk of lung cancer for carriers of the rs2107425 TT genotype (odds ratio = 1.599, 95%CI = 1.106–2.313, P = 0.013). In both dominant and recessive models, significant associations were found between rs2107425 and lung cancer risk, and the corresponding odds ratios were 1.346 (1.022–1.774) and 1.400 (1.011–1.937), with P values 0.035 and 0.043, respectively. There was no significant correlation between lung cancer risk and rs2735469, rs217727 and rs17658052. Interaction analysis showed that their combined effects had a greater impact on lung cancer than individual effects of polymorphism and cooking smoke exposure. However, further analysis showed that the both additive model and the multiplicative model were not statistically significant.ConclusionThe polymorphism rs2107425 in H19 gene was associated with the risk of lung cancer among female who never smokes in Shenyang, China.

The hSNM1B/Apollo variant rs11552449 is associated with cellular sensitivity towards mitomycin C and ionizing radiation

The polymorphism rs11552449 (c.181C > T, p.His61Tyr) in the hSNM1B/Apollo gene has been repeatedly shown to be associated with an increased risk for breast cancer. The aim of the current study was to investigate the association between rs11552449 and the degree of cellular sensitivity to mitomycin C (MMC) and ionizing radiation (IR). A total of 69 lymphoblastoid cell lines (LCLs) from generally healthy donors were tested for their sensitivity towards MMC and IR in growth inhibition experiments. LCLs heterozygous for rs11552449 were significantly more sensitive to MMC and IR than homozygous cells with the CC genotype (p < 0.05 and p < 0.01 for MMC and IR, respectively) and in the case of MMC also for the TT genotype (p < 0.01). Interestingly, heterozygous CT cells expressed significantly more full length hSNM1B/Apollo mRNA than cells with the homozygous CC (p < 0.0001) or TT genotypes (p < 0.00001). Thus, the observed higher sensitivity of cell lines heterozygous for rs11552449 towards MMC and IR may be a consequence of differential expression of hSNM1B/Apollo associated with rs11552449, a feature which has not been ascribed to this polymorphism before. Interestingly, relative leukocyte telomere length (rLTL) analyzed in a subset of these cells (N = 62) and in leukocytes of N = 1710 Berlin Aging Study II (BASE-II) participants was not associated with rs11552449. The results suggest that hSNM1B/Apollo is causal for the repeatedly reported association between rs11552449 and breast cancer. These results pave the way for further research regarding the clinical impact of rs11552449, e.g. on the clinical outcome of cancer therapy with DNA interstrand crosslinking agents and IR.