CG Genotype Research Articles

Association of Interleukin-6 Polymorphisms with Schizophrenia and Depression: A Case-Control Study.

Growing evidence suggests a crossover in genetic susceptibility to schizophrenia and depression. We aimed to investigate the association of the rs1800795 and rs1800796 polymorphisms of the IL-6 gene with schizophrenia and depression in the Han Chinese population, combined with IL-6 serum levels. Gene sequencing and enzyme-linked immunosorbent assay were performed on 113 subjects with schizophrenia, 114 subjects with depression, and 110 healthy controls. Our findings showed that IL-6 concentrations in schizophrenia and depression groups were significantly higher than in the control group. The rs1800796 CC genotype and C allele were significantly associated with depression (P = .012 and P < .05, respectively). The rs1800796 CC and CG genotype was significantly associated with chronic schizophrenia (P = .020 and P = .009, respectively). Regarding the rs1800795 polymorphism, only one case of CG genotype was detected. The remainder were of the GG genotype. The IL-6 rs1800796 might serve as a protective factor for depression and schizophrenia in the Han Chinese population.

PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients

Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan–Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan–Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival.

Relation between latrophilin 3 (LPHN3) gene polymorphism (rs2345039) and attention deficit hyperactivity disorder in children

BackgroundThe most prevalent psychological disorder in children is attention deficit hyperactivity disorder (ADHD). Latrophilin 3 (LPHN3) is a G protein-coupled receptor family member. It is brain specific and related to attention deficit hyperactivity disorder (ADHD) genetic susceptibility. This study aimed to assess the association of LPHN3 gene with ADHD and its types.MethodsThe subjects were 2 groups: group I, thirty patients with ADHD, and group II, thirty healthy individuals as a control group. The process of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to establish the genetic association of ADHD with the polymorphic gene LPHN3 (rs2345039).ResultsThe ADHD group included 20 male and 10 females; the mean age was 9.8±1.8 years. LPHN3 rs2345039 polymorphism genotypes distribution showed a statistical significant difference between ADHD and controls (P = 0.01). In the ADHD group, individuals with CG genotype were 5.8-folds to have ADHD than CC individuals. Also, those with GG genotype were about six times more likely to have ADHD than CC ones. All of these relationships were significant statistically (P = 0.024 and = 0.018, respectively). Individuals carrying the G allele were 2.6 times more likely to develop ADHD than those carrying the C allele (OR = 2.6, 95% CI = 1.3–5.6, P value = 0.01).ConclusionOur results demonstrate an association between latrophilin 3 (LPHN3) gene rs2345039 and ADHD. Moreover, LPHN3 polymorphisms tend to have a key role in triggering the condition and exacerbating its severity.

In Silico and In Vitro Analyses of PNPLA3 rs738409 C&gt;G Polymorphism in Patients With Non-alcoholic Fatty Liver Disease

Background: The polymorphism associated with liver fat content, which is well-known as PNPLA3 rs738409 (Patatin-like phospholipase domain-containing protein 3), is one of the critical subjects widely investigated in the literature regarding the prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide. The present research aimed to study the bioinformatics investigations of this polymorphism together with the in vitro analyses among patients with NAFLD. Materials and Methods: In this case-control study, after performing bioinformatics analysis, the laboratory examination was performed in several steps. Genomic DNA was extracted from the blood of 53 NAFLD patients and 107 subjects with normal liver ultrasounds. PNPLA3 rs738409 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The laboratory test results, including fasting blood sugar, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase were collected from medical records. Finally, statistical analysis was performed using SPSS software, version 18.0. Results: The frequency of the G allele was 56% and 36% among patients and in the control group, respectively. The frequency of genotypes was 35.8% and 47.7% (CC), 17% and 31.8% (CG), 47.2% and 20.6% (GG) in patients and control groups, respectively. The adjusted odds ratios for PNPLA3 rs738409 C&gt;G were 3.0 (95% confidence interval [CI]: 1.28-6.98, P=.011) and 0.68 (95% CI: 0.25- 1.83, P = .44) for GG and CG genotypes, respectively. Conclusion: The findings showed the association between the GG genotype and the presence of NAFLD. Furthermore, the bioinformatics findings suggested the probable risk of the disease incidence regarding the change of hydropathic characteristics resulting from the amino acid substitution.

Interactions of CDKAL1 rs7747752 polymorphism and serum levels of L-carnitine and choline are related to increased risk of gestational diabetes mellitus

BackgroundInteractions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1(CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM.MethodsA nested case-control study of 207 GDM women and their one-to-one, age-matched controls was organized from a prospective cohort of pregnant women in Tianjin, China. Conditional logistic regressions were used to test associations between CDKAL1 rs7747752 and serum levels of L-carnitine, choline, and betaine, and the risk of GDM. Additive interactions were performed to examine interactive effects of rs7747752 and low serum levels of L-carnitine, choline, and betaine on the risk of GDM.ResultsThe CDKAL1 rs7747752 G > C was associated with GDM in additive, dominant, and recessive model (P <0.05). The rs7747752 CC genotype enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 6.14 (2.61–14.4) to 19.6 (5.65–68.1) and the OR of choline ≤ vs. > 110 nmol/mL from 2.37 (1.07–5.28) to 12.1 (3.22–45.6), with significant additive interactions. Similarly, CG genotype also enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 4.70 (2.01–11.0) to 11.4 (3.98–32.9), with a significant additive interaction. However, the additive interaction between rs7747752 and betaine ≤ 200 nmol/mL on the risk of GDM was not significant.ConclusionsThe CC or CG genotype carriers in rs7747752 of CDKAL1 who have a low serum level of L-carnitine or choline are at a particular high risk of GDM. Randomized controlled trials are warranted to test the effect of supplement of L-carnitine or choline on the risk of GDM in the high-risk group.

PSXII-6 Evaluation of the Influence of bGH Gene Polymorphism on Elemental Composition of Blood Serum and Beef Productivity of Black Spotted Bulls

Abstract The purpose of this study was to establish the effect of single-nucleotide polymorphism of the bovine growth hormone (bGH) gene on elemental status and beef productivity of Black Spotted bulls (n=100; age-18 months). DNA samples were isolated from whole blood. The bGH gene polymorphism was determined using the PCR-RFLP method followed by restriction analysis. The elemental composition of the samples was estimated according to 25 chemical elements (Al, As, B, Ca, Cd, Co, Cr, Cu, Fe, I, K, Li, Mg, Mn, Na, Ni, P, Pb, Se, Si, Sn, Hg, Sr, V, Zn) by ICP AES and ICP MS. The detection of SNP (rs135322669) in the bGH gene showed three genotypes: CC (n=58), CG (n=24), GG (n=18). A comparative analysis showed that blood serum of animals with CC genotype contained significantly (Р£0.05) more Co, Cr, Cu, Fe, Ca, I, Se, Si, Li, Sr compared to the CG and Cu, I genotypes, Se, Ca, Si, Li, V, Sr in comparison with the GG genotype. In bulls with genotype CG to GG more toxic elements-Al, Sn, Pb were accumulated significantly (P£0.01). The Black Spotted bulls with the CC genotype advanced over animals with CG and GG, according to fresh carcass weight by 5.1 (Р≤0.05) and 8.9% (Р≤0.05), carcass yield-by 0.38 and 0.91% (Р≤0.05), internal fat mass-by 5.9 (Р≤0.05) and 15.6% (Р≤0.01), slaughter weight-by 4.8 (Р≤0.05) and 9.1% (Р≤0.01), slaughter yield-by 0.51 and 1.2% (Р≤0.05), pulp weight-by 5.4 (Р≤0.05) and 10.8% (P≤0.01). Thus, selecting Black Spotted bulls according to the bGH gene polymorphism, it is advisable to select individuals homozygous for the CC genotype. Animals with the indicated genotype are characterized by higher beef productivity, increased metabolism of essential elements and a minimum quantity of toxic elements in relation to animals with the CG and GG genotypes.

Analysis of Common Mutation of P53 Gene in Male with Lung Cancer in Mosul City

TP53 gene plays a critical role in the follow-up of different cancer cases, including diagnosis and follow-up treatment and the mutation in the P53 gene. It harms the encoded P53 protein and the less function of P53 protein in different types of cancer due to the mutation in the TP53 gene. P53 protein has many mechanisms to eliminate cancer cells, like apoptosis, cell cycle arrest, and DNA repair. This study aims to detect the abnormality change in the sequence of P53 mutation and the correlation with cancer in Mosul city DNA extraction depends on the manual description from blood, the Pro72Arg in exon 4 G\C allele mutation measurement by ARMS-PCR, and the analysis of common mutation in Exon 3,4,5 by DNA sequencing technique. The result of this study shows the observation of different genotypes and allelic frequencies of Pro72Arg polymorphism in exon 4. It was the presence of wild-type genotype CC (pro\pro) 12%, hetero genotype CG (pro\arg) 72% and mutant genotype GG (arg\arg) 16% in patients with Lung cancer. While in healthy people, the wild genotype CC was 26 hetero genotype CG 66 and mutant genotype GG 8%. As for the result of DNA sequencing, this research doesn't find any change in the nucleotide of Exon 5 for the P53 gene of the case study. At the same time, the DNA sequence result of Exon 6 for the P53 gene in patients finds some changes in the nucleotide sequence with sequence. According to this study, the observation of different genotypes and allelic frequency of Pro72Arg polymorphism in exon 4 for the P53 gene present significant variation between patients with lung cancer and healthy group male with Lung cancer Keywords: P53 gene, ARMS-PCR, Mutation, SNP, Lung cancer, Exon.

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population.

Bladder cancer (BCa) is an increasingly severe clinical and public health issue. Therefore, we aim to investigate BCa susceptibility loci in the Chinese population. In this study, 487 BCa patients and 563 controls were recruited from the First Affiliated Hospital of China Medical University from July 2015 to September 2020. A total of ten single-nucleotide polymorphisms (SNPs) in solute carrier family 15 member 1 (SLC15A1), CWC27 spliceosome associated cyclophilin (CWC27), or UDP glucuronosyltransferase family 1 member A3 (UGT1A3) genes were genotyped. The associations between the candidate SNPs and BCa were analyzed using genotype and haplotype analysis. The results demonstrated that Rs4646227 of SLC15A1 has a significant association with BCa. The patients with CG (OR =2.513, p < 0.05) and GG (OR =2.859, p < 0.05) genotypes had an increasing risk of BCa compared with the CC genotype. For the CWC27 gene, genotypic frequency analysis revealed that the GT or TT genotype of rs2042329 and the CT or TT genotype of rs1870437 were more frequent in BCa patients than those in the control group, indicating that these genotypes were associated with a higher risk of BCa (all p < 0.05). Haplotypes of SLC15A1, UGT1A3, and CWC27 genes found that the C-C-C haplotype of SLC15A1 was associated with a lower risk of BCa while the C-G-C haplotype was associated with a higher risk. For the UGT1A3 gene, a moderate protective effect was observed with the most frequent T-T-C haplotype, and for the CWC27 gene, most of the haplotypes showed no association with BCa, except the G-G-C-T haplotype (order of SNPs: rs2042329-rs7735338-rs1870437-rs2278351, OR =0.81, p =0.038). In sum, this study indicated that rs2042329 and rs1870437 in the CWC27 gene and rs4646227 in the SLC15A1 gene are independent indicators for BCa risk in Chinese people. Further large-scale studies are required to validate these findings. Also, this study provided the theoretical basis for developing new therapeutic drug targeting of BCa.

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis.

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants—SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters’ SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

Association of the IL-6 gene rs1800796 polymorphism with recurrent pregnancy loss in a population of women from northwestern China: a case-control study

We aimed to identify whether IL-1β (rs1143627, rs1143634 and rs16944), IL-6 (rs1800796), IL-10(rs1800872 and rs1800896), and vascular endothelial growth factor (VEGF) (rs1570360) gene polymorphisms were risk factors for recurrent pregnancy loss (RPL) in a population of women in northwestern China. A total of 150 women with a history of two or more unexplained and consecutive spontaneous abortions before their 24th gestational week and 150 age-matched women with at least two normal pregnancies and no history of pregnancy loss were included in the present study as cases and controls, respectively. We extracted genomic DNA from peripheral blood, and executed genotyping with the SNaPshot technique. Logistic regression analysis was conducted to determine the odds ratios (ORs) of the associations between the polymorphisms and RPL. Of the seven polymorphisms we studied, only IL-6 rs1800796 showed a statistically significant association with RPL, as we noted an elevated risk of RPL with the G allele (OR = 1.57; 95% CI, 1.10–2.24; p = .01). The risk of RPL in women with the GG + CG genotype (OR = 1.96; 95% CI, 1.19–3.21; p = .01) was also higher than that in women with the CC genotype. The present study thus indicated that the IL-6 gene rs1800796 polymorphism may serve as an important risk factor for RPL in this group of women from northwestern China. IMPACT STATEMENT What is already known on this subject? Cytokine and vascular endothelial growth factor (VEGF) gene polymorphisms may affect the risk of recurrent pregnancy loss (RPL) by modulating cytokine and VEGF expression. What do the results of this study add? The study results showed that the IL-6 rs1800796 single-nucleotide polymorphism constituted a risk factor for RPL in a population of women in northwestern China. What are the implications of these findings for clinical practice and/or further research? This study clearly reflects clinical significance as it provides a theoretical basis for the early screening of RPL by revealing that the IL-6 gene rs1800796 polymorphism increased the risk of RPL in women in northwestern China.

Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

BackgroundInsulin receptor substrate‐1 (IRS‐1) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes. CYP2C19*2 (rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between IRS‐1, CYP2C19*2 genotypes, platelet reactivity, and 1‐year outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.Methods and ResultsGenotyping was performed using an improved multiplex ligation detection reaction technique. Platelet aggregation was assessed by light transmission aggregometry. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke. A total of 2213 consecutive patients were screened and 1614 were recruited. At 1 month, patients with IRS‐1 CG genotype had significantly lower levels of ADP‐induced platelet aggregation compared with patients with CC homozygotes. Patients with IRS‐1 CG or GG genotype had a 2.09‐fold higher risk of major adverse cardiovascular events compared with those with CC homozygotes (95% CI, 1.04–4.19; P=0.0376). By comparison, patients with CYP2C19*2 GA or AA genotype had higher ADP‐induced platelet aggregation compared with patients with GG homozygotes. Although there was no significant difference in risk of major adverse cardiovascular events between patients with GA/AA and GG genotypes, patients with GA genotype had a 2.19‐fold higher risk than those with GG homozygotes (95% CI, 1.13–4.24; P=0.0200). No interaction between IRS‐1 and CYP2C19*2 genotypes was observed.ConclusionsIn patients following percutaneous coronary intervention, IRS‐1 GG/CG and CYP2C19*2 GA genotypes were associated with 2.09‐ and 2.19‐fold increased cardiovascular risk, respectively, at 1‐year follow‐up. The association between IRS‐1 genotypes and major adverse cardiovascular events appeared to be independent of known clinical predictors.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01968499.

A significant association between rs2295190 polymorphism of the ESR1 gene and fibromyalgia syndrome

Fibromyalgia syndrome (FMS) is a multifactorial disease characterized by chronic diffuse pain. Genetic factors are also involved in the etiology. However, there is not enough information on the genetic factors that play a role in the pathogenesis of FMS. The aim of this study is to investigate the relationship between estrogen receptor 1 gene (ESR1) 594G>A (rs2228480) and 325C>G (rs2295190) polymorphisms and fibromyalgia syndrome (FMS). A total of 294 women, 146 of who were FMS patients and 148 of whom were healthy controls, were enrolled in the study. The instruments used to collect data from patients included patient follow-up form, Visual Analogue Scale (VAS), and Fibromyalgia Impact Questionnaire (FIQ). Genotyping of ESR1 594G>A and 325C>G polymorphisms in the extracted DNA samples was performed using an RT-PCR device and TaqMan hydrolysis probes. It was found that, for rs2295190 polymorphism, patients with CG and GG genotypes versus CC genotypes showed a decreased risk for FMS (OR: 0.442; 95% CI: 0.234-0.833). But there were no significant differences were found in the genotype distribution of rs2228480 polymorphism between the FMS patients and controls. The intragroup evaluation of FMS patients revealed no significant association between symptoms, pain score, FIQ score, and polymorphisms (p>0.05). We are of the opinion that there is a significant association between ESR1 rs2295190 polymorphism and FMS and that this polymorphism may be protective against FMS. However, there is a need for comprehensive studies on different populations to obtain clearer data as well as further studies to elucidate the possible mechanism of association.

Towards Sustainable Sources of Omega-3 Long-Chain Polyunsaturated Fatty Acids in Northern Australian Tropical Crossbred Beef Steers through Single Nucleotide Polymorphisms in Lipogenic Genes for Meat Eating Quality

This study aimed to identify single nucleotide polymorphisms (SNP) in lipogenic genes of northern Australian tropically adapted crossbred beef cattle and to evaluate associations with healthy lipid traits of the Longissimus dorsi (loin eye) muscle. The hypothesis tested was that there are significant associations between SNP loci encoding for the fatty acid binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD) and fatty acid synthase (FASN) genes and human health beneficial omega-3 long-chain polyunsaturated fatty acids (ω3 LC-PUFA) within the loin eye muscle of northern Australian crossbred beef cattle. Brahman, Charbray, and Droughtmaster crossbred steers were fed on Rhodes grass hay augmented with desmanthus, lucerne, or both, for 140 days and the loin eye muscle sampled for intramuscular fat (IMF), fat melting point (FMP), and fatty acid composition. Polymorphisms in FABP4, SCD, and FASN genes with significant effects on lipid traits were identified with next-generation sequencing. The GG genotype at the FABP4 g.44677239C&gt;G locus was associated with higher proportion of linoleic acid than the CC and CG genotypes (p &lt; 0.05). Multiple comparisons of genotypes at the SCD g.21266629G&gt;T locus indicated that the TT genotype had significantly higher eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids than GG genotype (p &lt; 0.05). Significant correlations (p &lt; 0.05) between FASN SNP and IMF, saturated and monounsaturated fatty acids were observed. These results provide insights into the contribution of lipogenic genes to intramuscular fat deposition and SNP marker-assisted selection for improvement of meat-eating quality, with emphasis on alternate and sustainable sources of ω3 LC-PUFA, in northern Australian tropical crossbred beef cattle, hence an acceptance of the tested hypothesis.

Association of Paraoxonase-2 (C1053G) Gene Polymorphism with the Expression of Paraoxonase-2 Gene in Patients of Ischemic Stroke - A Pilot Study in Indian Population.

Oxidative stress plays an important role in atherosclerosis and ischemic stroke. Due to antioxidant properties of Paraoxonase-2, we studied the implication of Paraoxonase-2 gene polymorphism (C1053G) on expression of Paraoxonase-2 gene at mRNA level in ischemic stroke patients. 40 patients of ischemic stroke and 40 age and sex-matched controls were included. Paraoxonase-2 genotypes were evaluated by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and expression of Paraoxonase-2 gene at mRNA level was determined by quantitative real time Polymerase Chain Reaction analysed as delta-CT (△CT). The observed allele frequencies in patients for C and G allele were 0.61 and 0.39 respectively, and were 0.72 and 0.28 in control group. No significant association was found in C allele of C1053G polymorphism and ischemic stroke. The average △ CT value is significantly (p = 0.0001) higher in patients group (7.68 ± 2.0) as compared to controls (5.70 ± 1.8). We found a significant difference in the average delta-CT value (p = 0.0001), wherein down-regulated paraoxonase-2 gene expression (approximately 0.25 fold) was observed in case of patients as compared to controls. Down-regulated expression of paraoxonase-2 gene was observed in patients with GG genotype as compared to CG and CC genotypes in patients with ischemic stroke (p = 0.0001). Down-regulated Paraoxonase-2 gene expression, as evidenced by low mRNA levels in GG genotype may be one of the contributory factors in the progression of ischemic stroke.

The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics.

BackgroundThe MTNR1B gene encodes a receptor for melatonin, a hormone regulating biorhythms. Disruptions in biorhythms contribute to the development of type 2 diabetes mellitus (T2DM). Genetic studies suggest that variability in the MTNR1B gene affects T2DM development. Our aim was to compare the distribution of the genetic variant rs10830963 between persons differing in glucose tolerance in a sample of the Czech population (N=1206). We also evaluated possible associations of the polymorphism with insulin sensitivity, beta cell function, with the shape of glucose, insulin and C-peptide trajectories measured 7 times during a 3-hour oral glucose tolerance test (OGTT) and with glucagon response. In a subgroup of 268 volunteers we also evaluated sleep patterns and biorhythm.Results13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women.ConclusionIn a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

Indicators of Immune and Neurohumoral Profile in Women of Fertile Age with Functional Disorders of the Autonomic Nervous System Associated with Polymorphic Variants of the HTR2A (rs7997012) and TP53 (rs1042522) Genes.

In women of fertile age with functional disorders of the autonomic nervous system (ANS), a complex of indicators of the immune and neurohumoral profile associated with polymorphic variants of the HTR2A (rs7997012) and TP53 (rs1042522) genes was revealed. In patients with the diagnosis "G90.8. Other disorders of the autonomic nervous system", the neurohumoral profile is characterized by excessive content of cortisol and serotonin (p<0.05), which indicates the development of the hypersympathicotonic variant of autonomic regulation disorders. The cellular immune profile in the examined individuals was characterized by a significant decrease in the content of CD3+CD4+ and CD3+CD8+ lymphocytes (p<0.05). At the same time hyperactivation of the humoral immune response was observed. In particular, we revealed enhanced production of IgG and IgM antibodies accompanied by increased count of CD19+ lymphocytes (p<0.05), which characterized clinical and laboratory manifestations of the asthenic syndrome. The women with ANS disorders had increased frequency of the G allele (OR=3.00; 95%CI 1.20-7.47) and GG genotype (OR=3.91; 95%CI 1.00-15.24) of the HTR2A (rs7997012) serotonin receptor gene, as well as the G allele (OR=1.93; 95%CI 1.04-3.57), CG genotype (OR=2.38; 95%CI 1.02-5.53) and the GG genotype (OR=1.48; 95%CI 0.42-5.24) of the TP53 (rs1042522) oncosuppressor protein gene (p<0.05). The polymorphic G allele and GG genotype variants of candidate genes (HTR2A (rs7997012) and TP53 (rs1042522) genes) in women with ANS pathology are associated with an imbalance of the neurohumoral (excess of cortisol and serotonin) and immune regulation (deficiency of the CD3+CD4+ and CD3+CD8+, excess of CD19+, IgG and IgM). These parameters form a complex of the immune, neurohumoral, and genetic profile indicators in women of fertile age that characterize functional disorders of ANS manifestations by hypersympathicotonic type with an asthenic component.

Association between IL-22 polymorphism (Rs1179251) and outcomes of HBV infection

BackgroundGenetic variations can play an essential role in the modulation of immune system responses. Interleukin-22 (IL-22) is a recently discovered cytokine of the IL-10 family that can affect the immune response to cancer, inflammation, and infections. Therefore, its polymorphisms might influence the HBV infection outcome. AimThis study aimed to evaluate rs1179251 single nucleotide polymorphism in the IL-22 gene as a host genetic factor and its effect on hepatitis B infection outcome. MethodsDNA was extracted from 100 HBV-infected patients with cirrhotic/hepatocellular carcinoma (C/HCC), 100 patients with chronic active hepatitis (CAH), 100 asymptomatic healthy carriers (HC) and 58 individuals that their infection was spontaneously cleared (SC). IL-22 rs1179251 single nucleotide polymorphism (SNP) was then genotyped in all cases using PCR-RFLP method. ResultsThe results of rs1179251 genotyping demonstrated that G allele in HC (30%) was significantly more frequent than CAH group (17%) (P = 0.003). HC cases also inherited more CG genotype (46%) than CAH group (28%) (P = 0.006) but less GG genotype (7%) than SC group (13.8%) (P = 0.01). ConclusionOur findings collectively suggest that CG and GG genotype or generally G allele of rs1179251 in IL-22 gene might have a protective role against HBV infection. However how it can be involved in the immune system to deactivate the virus remained to be elucidated.

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) serum level and genetic polymorphisms associated with cutaneous leishmania infections

IntroductionCutaneous leishmaniasis is considered a parasitic contagion resulting from the flagellated parasite belonging to the genus of Leishmania. Also, cutaneous leishmaniasis is a zoonotic ailment transmitted through the bloodsucking sand-flies bite (belonging to the Phlebotomus genus). The disease's reservoirs included wild or semi-domesticated animals, in general rodents and dogs. Tissue inhibitor metalloproteinase-1 (TIMP-1) is one of the extracellular matrix proteins that have a role in vessel wall degeneration and aneurysm development. In addition, it belongs to the zinc-dependent endopeptidases family that are involved in the degradation of connective tissues proteins which are included in vascular integrity maintenance. The Genetic deviations in the TIMP-1 genes might impact their expression at the transcription level or the enzyme activity. Therefore, the present study aimed to detect the impact of TIMP-1 serum level and single nucleotide polymorphisms (SNPs) rs41454248 and rs1043428 among the cutaneous leishmaniasis patients’ group compared to the control group. SubjectsSeventy-five cutaneous leishmaniasis patients (39 males and 36 females) with the age mean 23.91 ± 13.14 years participated in this study, compared to the matched number, age, and gender of a healthy control group (75: 38 males and 37 females) with the age mean 22.84 ± 4.35 years. In the current study, the serum level of TIM-1 and rs41454248 and rs1043428 SNPs were studied among the cutaneous leishmaniasis patients’ group compared to the control group. ResultsThe findings of the TIMP-1 level referred to a significant decrease among the cutaneous leishmaniasis patients’ group compared to the healthy control group (26339.67 ± 900.79 vs. 33480.25 ± 1098.63). Such, the rs41454248 SNPs findings referred that the GG genotype and G allele were non-significantly increased frequency percentage in cutaneous leishmaniasis patients group compared to the healthy control group (29.33 vs. 18.67%, OR: 1.81, p = 0.180; 55.0 vs. 47.0%, OR: 1.38, p = 0.204 respectively). Also, the high OR value of GG genotype and G allele referred to this genotype and allele might be a risk factor for cutaneous leishmaniasis. Likewise, the findings of rs1043428 SNPs appeared that the CC genotype and C allele were significantly increased frequency percentage in cutaneous leishmaniasis patients' group compared to the control group (37.33 vs. 4.0%, OR: 14.30, p = 3.6 × 10−7; 57.0 vs. 21.33, OR: 4.82, p = 4.5 × 10−10). Also, the high OR value of CC genotype and C allele referred to this genotype and allele might be risk factors for cutaneous leishmaniasis. In addition, the CG genotype appeared a non-significant increased frequency percentage in the patients' group compared to the control group and the value of OR referred to might be a risk factor for cutaneous leishmaniasis (33.33 vs. 25.33, OR: 1.47, p = 0.370). In addition, the serum level of TIMP-1 with the rs41454248 was significantly decreased in GA and AA genotypes of the patients’ group compared to the control. While the level was non-significantly decreased in the GG genotype of the patients' group compared to the control group. Likewise, the level of TIMP-1 with the rs1043428 was non-significantly decreased in all genotypes (except TT genotype) of the patients' group compared to the control. Whereas, a significant decrease level was appeared in the TT genotype of the patients' group compared to the healthy control group. ConclusionThe current findings demonstrated a significant association between TIMP-1 serum level and genetic polymorphisms (rs1043428 and rs41454248) among cutaneous leishmaniasis patients.

Contribution of polymorphism of genes of aldosterone synthetase CYP11B2 (C-344T), adrenergic receptors type 1 ADRB1 (Gly389Arg) and type 2 ADRB2 (Arg16Gly) to formation of different obesity phenotypes

Objective. To study the relationship of polymorphism of the genes of aldosterone synthetase CYP11B2 (C-344T), adrenergic receptor type 1 ADRB1 (Gly389Arg) and type 2 ADRB2 (Arg16Gly) with the risk of obesity.&#x0D; Materials and methods. The study involved 170 patients; the mean age was 45.4 7.3 years. The patients were divided into 2 groups: group 1 obese patients with metabolic disorders in combination with 1-2 degree hypertension complicated obesity (n = 90); group 2 50 participants with obesity without metabolic disorders (metabolically healthy obesity). The control group consisted of 100 healthy respondents. All the surveyed persons underwent anthropometry and general clinical studies according to the recommendation for examination of patients with obesity and arterial hypertension. Total DNA was isolated from venous whole blood samples by RT-PCR using the DNA-Sorb-B kit. &#x0D; Results. It was found that in the group of complicated obesity, the carriage of the TT genotype of the CYP11B2 gene polymorphism (C-344T) and the CG genotype of the Gly389Arg polymorphism of the ADRB1 gene prevailed in comparison with the group of metabolically healthy obesity and healthy respondents. The predominance of carriage of the GG genotype of the ADRB2 gene polymorphism (Arg16Gly) was revealed in the groups of metabolically healthy obesity and complicated obesity in comparison with the healthy group. An association of the polymorphic position of the ADRB1 (Gly389Arg) and ADRB2 (Arg16Gly) genes with the level of low-density lipoprotein cholesterol, triglycerides, the level of systolic blood pressure and diastolic blood pressure, and the level of uric acid was established. The relationship between the polymorphism of the CYP11B2 (C-344T) promoter region and the level of glomerular filtration rate and total cholesterol was determined.&#x0D; Conclusions. Analysis of ADRB1 (Gly389Arg), ADRB2 (Arg16Gly), and CYP11B2 (C-344T) gene polymorphism variants can be used as an additional marker to assess the risk of developing obesity, arterial hypertension, and metabolic disorders.