Associationj of TSHR Gene Single Neucleotide Intronic Polymorphism with the Risk of Hypothyroid and Hyperthyroid Disorders in Yazd Province.

The present study was carried, for the first time, out to evaluate the association of rs2268458 polymorphism, biochemical and environmental factors on hypothyroid and hyperthyroid disorders in thyroid patients and healthy individuals in Yazd province, Iran. In this study, blood samples were collected from a total of 100 cases, including 60 hypothyroid, 20 hyperthyroidism individual cases and 20 normal individuals. DNA was extracted from blood samples and the rs2268458 single neucleotide intronic polymorphism was evaluated using RFLP-PCR. The results have shown that 59 cases were homozygote (TT), 40 cases heterozygote (TC) with one homozygote (CC) case, as follows; A total of 25 (TT) homozygote cases were observed to be hypothyroid females, 20 (TC) heterozygote cases of hypothyroid females, 7 (TT) homozygote male hypothyroid cases and 7 (TC) heterozygote male hypothyroid cases and 1 (CC) homozygote male hypothyroid patient. While, 7 (TT) homozygote hyperthyroid female cases, 8 (TC) heterozygote hyperthyroid female cases,were also observed. According to our study, heterozygote cases (TC) showed less severe symptoms, while homozygote cases (TT) showed no serious symptoms and the (CC) homozygote case (CC) showed severe thyroid abnormality symptoms. So, it can be concluded that the TSHR-related rs2268458 polymorphism is associated with hypothyroidism and hyperthyroidism in the male and female polulations of Yazd Province, Iran and C allele can be a risk factor for some physio-biochemical and hormonal imbalance in the thyroid disorder patients.

Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer,and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated <i>FOXO3</i> gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (<i>p</i> = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69–1.26, <i>p</i> &#x3e; 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (<i>p</i> &#x3c; 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in <i>FOXO3</i> (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.

The Immunoregulatory Role of the Signal Regulatory Protein Family and CD47 Signaling Pathway in Type 1 Diabetes

BackgroundThe pathogenesis of type 1 diabetes (T1D) involves complex genetic susceptibility that impacts pathways regulating host immunity and the target of autoimmune attack, insulin-producing pancreatic β-cells. Interactions between risk variants and environmental factors result in significant heterogeneity in clinical presentation among those who develop T1D. Although genetic risk is dominated by the human leukocyte antigen (HLA) class II and insulin (INS) gene loci, nearly 150 additional risk variants are significantly associated with the disease, including polymorphisms in immune checkpoint molecules, such as SIRPG.Scope of ReviewIn this review, we summarize the literature related to the T1D-associated risk variants in SIRPG, which include a protein-coding variant (rs6043409, G&gt;A; A263V) and an intronic polymorphism (rs2281808, C&gt;T), and their potential impacts on the immunoregulatory signal regulatory protein (SIRP) family:CD47 signaling axis. We discuss how dysregulated expression or function of SIRPs and CD47 in antigen-presenting cells (APCs), T cells, natural killer (NK) cells, and pancreatic β-cells could potentially promote T1D development.Major ConclusionsWe propose a hypothesis, supported by emerging genetic and functional immune studies, which states a loss of proper SIRP:CD47 signaling may result in increased lymphocyte activation and cytotoxicity and enhanced β-cell destruction. Thus, we present several novel therapeutic strategies for modulation of SIRPs and CD47 to intervene in T1D.

Association of the Intronic Polymorphism rs3773364 A>G in Synapsin-2 Gene with Epilepsy Patients in Iraq

Epilepsy is a central nervous system disease which is characterized by a recurrent seizure that distinguishes it from other similar diseases. Epilepsy may occur due to defects in genes that encode some receptors in the brain. For this reason, this study aimed to understand the association between Synapsin-2 (SYN2) gene and susceptibility to epilepsy. Blood samples were collected from 40 volunteers, including 30 patients suffering epilepsy with an age range of 26-49 years old and 10 healthy individuals with an age range of 25-53 years old. The study sample involved 16 males and 14 females with epilepsy along with 6 males and 4 females healthy subjects. DNA was isolated from the volunteers for PCR-RFLP assay. Genotyping of rs3773364 A>G SYN2 was conducted and the results refer to a highly significant difference in the distribution of AG genotype (P=0.0001), while there is no significant difference in the distribution of AA and GG genotypes, with p values of 0.1702 and 1.00, respectively. The results also showed that gender did not significantly affect the results when comparing patients with the control (p=0.0934). Our findings indicates that SYN2 rs3773364 A>G confers risk to epilepsy and may be implicated in epileptogenesis.

Association of the CFTR gene with asthma and airway mucus hypersecretion

Introduction Asthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of those studies have been questioned for their numerous limitations and contradictory results. Objectives (1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion. Method Comparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis. Results Genetic differences were observed in the c.1680-870T>A polymorphism of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p = 0.036). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011). Conclusion The results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in the CFTR gene (NM_000492.3:c.1680-870T>A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype.

Analysis of 13 TP53 and WRAP53 polymorphism frequencies in russian populations

In the last decade the search for and annotation of human genome polymorphisms associated with phenotype have become particularly important concerning the opportunity of their use in medical and population genetics, pharmacogenomics and evolutionary biology. The study was aimed to calculate the frequencies and analyze the prevalence of 13 germline polymorphisms of two genes, ТР53 encoding the genome-keeper p53 protein and WRAP53 involved in regulation of p53 production, in 28 Russian populations. We obtained data on 9 exonic ТР53 variants (rs587781663, rs17882252, rs150293825, rs112431538, rs149633775, rs144340710, rs1042522, rs1800371, rs201753350), one intronic polymorphism (rs17881850), and three variants of WRAP53 (rs17880282, rs2287499, rs34067256). In the majority of populations the sample size was over 50 people (except five populations with 30–49 surveyed people). The alternative alleles’ population frequencies for studies genetic variants in most Russian populations were close to appropriate allele frequencies in European and Asian populations of similar origin taken from global databases. The exceptions were six populations ("Central Caucasus", "Dagestan", "northern Russians", "southeastern Russians", "Tatars" and "Transcaucasia") with increased alternative alleles’ population frequencies. All listed populations except the population of “southeastern Russians” are characterized by polymorphisms with high allele frequencies not satisfying the Hardy–Weinberg principle.