Single Nucleotide Polimorphisms Research Articles

Single nucleotide polimorphisms of the main glutamate transporter in the brain are associated with lower regional brain glucose metabolism in cognitively impaired individuals

Single nucleotide polimorphisms of the main glutamate transporter in the brain are associated with lower regional brain glucose metabolism in cognitively impaired individuals

Single nucleotide polimorphisms of the main glutamate transporter in the brain are associated with lower regional brain glucose metabolism in cognitively impaired individuals

Single nucleotide polimorphisms of the main glutamate transporter in the brain are associated with lower regional brain glucose metabolism in cognitively impaired individuals

Association between single nucleotide polymorphisms in oxytocin and vasopressin receptor genes and symptom severity of autism spectrum disorder– preliminary study

IntroductionOne of the defining features of autism spectrum disorder (ASD) are deficits in social interaction and communication. Although their etiology is poorly understood, several lines of evidence from studies on humans and rodents suggest that two nonapeptides – oxytocin and vasopressin – might play a pivotal role in their development.ObjectivesTo evaluate if single nucleotide polimorphisms in OXTR and AVPR1A genes are linked to the severity of symptoms in autism spectrum disorder.MethodsThe study was conducted on the group of 40 Caucasian males with average age of 14,22 (SD: 1,71) years. ADOS-2 examination was utilized for confirmation of ASD diagnosis as well as evaluation of symptoms severity in each patient. The genotyping of preselected SNPs for each gene (rs10877969; rs7294536; rs2254298; rs53576) was conducted.Results“CC” genotype at rs7294536 (p=0,033) was significantly associated with higher outcomes of ADOS-2 especially in terms of social affect. In case of oxytocin receptor gene, frequency of “AA”/”AG” genotype at rs2254298 equaled 100% and of “AA”/”AG” genotype at rs53576 equaled 85% of the study group (expected “A” allele frequency in neurotypical European population was respectively 11% and 35% according to 1000Genomes database). For rs10877969 prevalence of “CC”/”CT” genotype equaled 95% while expected frequency of “C” allele in neurotypical European population was 13%.ConclusionsOverrepresentation of minor alleles at rs2254298, rs53576 and rs10877969 in patients with ASD might indicate their link to development of ASD. Furthermore, significant association between minor allele at rs7294536 and symptoms severity suggest potential role of arginine-vasopressin receptor deficiency in clinical picture of ASD.DisclosureNo significant relationships.

Identification of single nucleotide polimorphisms and restriction enzym on prolactin gene in Alabio and Mojosari duck

Prolactin plays important roles in avian reproduction as it induces broody behavior and regulates follicular development. The objectives of this study were to detect Single Nucleotide Polymorphisms (SNPs) of prolactin gene in Alabio and Mojosari ducks and determine the restriction enzymes for genotyping. Genomic DNA was isolated from 50 blood samples per each Alabio and Mojosari ducks. PCR amplification and sequencing were carried out to identify the SNP. In this study, SNP T-6068C was found based on three GenBank sequences alignment. Two SNPs (C-5796A and T-5817C) in intron 4 region were detected based on sequences of Alabio and Mojosari PCR products. Enzymes Fok1, BtsCI, BsrI were detected to recognize the SNP C-5796A. SNP T-6068C can be digested by enzym TspDTI. However no enzym was detected to recognize SNP T-5817C. In conclusion the SNPs detected from this study may be used in future studies to investigate the association of prolactin gene and egg production traits in Alabio and Mojosari ducks.

Intensive first-line triplet chemotherapy plus cetuximab FIr-C/FOx-C in RAS wild-type MCRC: Preliminary phase II data and prediction of individual limiting toxicity syndromes by pharmacogenomic biomarkers.

673 Background: Intensive first line bevacizumab added to triplet, and cetuximab (CET) to doublet in RAS wild-type MCRC significantly increased outcomes. We investigated safety/activity of FIr-C/FOx-C adding CET to triplet in RAS wild-type. Methods: Phase II study according to Simon two-step design: delta 15% (p070%, p185%), power80%, α5%, β20%; projected ORR I step 14/19. FIr-C/FOx-C: 5-fluorouracil (5-FU) 12h-TFI 900 mg/m2 days (d) 1-2,8-9,15-16,22-23 associated to weekly alternating irinotecan (CPT-11) 160 mg/m2 d1,15 or oxaliplatin 80 mg/m2 d8,22; CET loading dose, then 250 mg/m2 d1,8,15,22; every 28d. Toxicity, LTS evaluated/compared by chi-square test; activity/efficacy by log-rank. Pharmacogenomic biomarkers of 5-FU/CPT-11, 5-FU degradation rate (5-FUDR), Single Nucleotide Polimorphisms (SNP) ABCB1, CYP3A4, DYPD, UGT1A1, evaluated in individual patients with limiting toxicity syndromes (LTS) and at recommended dose. Results: 29 patients < 75 years, primary/intermediate CIRS. From April 2014, KRAS/NRAS wild-type eligible: median age 59; young-elderly (yE) 7, 24%; liver-limited (L-L) 7, 24%. Recommended CPT-11/5-FU doses 120/750 mg/m2. Activity met primary endpoint: OR 14/18 evaluable as-treated (76%), confirmed in preliminary phase II, 17/23 intent-to-treat (74%). Liver metastasectomies 14%, 57% L-L. At median follow-up 18 months, PFS 12, OS 23 months. At recommended doses, received DI > 80% for each drug; cumulative G3-4 toxicities: diarrhea 23%, asthenia 15%, vomiting 8%, hypertransaminasemy 8%; LTS, consisting of the LT, associated or not to G2 or other LT, in 19 patients (65.5%), 83% yE. LTS prevalently multiple than single site (59 vs 7% p0.006). Reduced FUDR, CYP3A4 and UGT1A1 SNPs, frequently associated, prevalently in patients with gastrointestinal LTS, while not without LTS. Conclusions: Intensive first-line FIr-C/FOx-C at recommended dose is tolerable, highly effective in RAS wild-type. Reduced FUDR, CYP3A4, UGT1A1 SNPs may predict individual LTS to select fit patients. Prospective studies will confirm efficacy and personalization by companion toxicity biomarkers. Clinical trial information: EudraCT 2009-016793-32.

Dopamine (D1) Receptors and Single Nucleotide Polimorphisms (SNPs) in Patients with Cognitive Impairment of Major Depressive Disorder (MDD).

A gene is the basic component of each chromosome in any cell of human body. It controls the heredity in human being and all other species. Adenine, Guanine, Thymidine and Cytosine (A, G, T, and C) are the bases of nucleotides that are ordered in a well-designed and in a proper sequence on the surface of each chromosome in the form of genes together with sugar and phosphate.

Epistatic interaction between TLR4 and NOD2 in patients with Crohn’s Disease: relation with risk and phenotype in a Spanish cohort

Crohn's Disease is one of the two major forms of the Inflammatory Bowel Diseases and, although the etiology is not completely understood, the confluence of environmental and genetic factors has been demonstrated. The aim of this study was to determine the distribution of TLR4 variants in a Spanish cohort of Crohn's Disease patients and their relation with phenotype and common NOD2 variants. A total of 371 Crohn's Disease (CD) patients and 636 healthy controls (HC) were included. Single Nucleotide Polimorphisms (SNPs) in TLR4 (D299G and T399I) and NOD2 (R702W and G908R) detection was performed by a Taqman(®) Allelic Discrimination Assay. 1007insC NOD2 variant was analyzed using a PCR combined with fluorescent technology and the different alleles were determined depending on the PCR products size. D299G and T399I were related to CD only in patients carrying NOD2 variants (NOD2+/TLR4+ haplotype) (p=0.036; OR=1.924), increasing the risk to develop CD when 1007insC and TLR4 variants were both present (OR=4.886). We also described a strong association between mutant NOD2 and CD risk (p<0.001, OR=3.214). R702W, G908R and 1007insC were associated when they were considered separately (p<0.001; p=0.002; p<0.001, respectively). Moreover, the patients carrying any mutant D299G or T399I polymorphisms were predisposed to develop a stricturing disease (p=0.013; OR=2.391), especially in the presence of NOD2 mutation (p=0.002; OR=4.989). In this study, ileal disease was also associated with the presence of at least one NOD2 susceptibility allele (p=0.001; OR=3.838) and, the risk of ileal CD was increased if TLR4 variants were presents (p<0.050; OR=4.160). TLR4 variants were related to bowel perforation, independently of NOD2.

Reelin Signaling Pathway Genotypes and Alzheimer Disease in a Spanish Population

Several reports suggest that the reelin protein could play a role in Alzheimer pathophysiology. This led us to ask whether genetic variability in the reelin pathway may increase the risk of developing Alzheimer disease (AD) or mild cognitive impairment (MCI). This was a case-control study in which neuropsychological tests were administered and peripheral blood samples taken. The study included 121 patients with AD, 94 with MCI, and 198 controls. Forty biallelic variants single nucleotide polimorphisms were genotyped in 8 genes related to reelin signaling pathway using a SNPlex genotyping system, and allele frequencies were compared between patients and controls using χ tests and obtaining odds ratios (OR). A total of 413 subjects with complete neuropsychological data were analyzed. A significant association between the genotypes RELN (rs528528 and rs2299356), PLK2 (rs15009 and rs702723), and CAMK2A (rs3756577 and rs3822606) and AD or MCI was found. A significant association also was found between the GG genotype at the RELN-rs2299356 and the risk of AD (OR=2.68, P=0.003) and between the AG genotype at the CAMK2A-rs3822606 (OR=2.13, P=0.004). We found a protective effect of the RELN-rs528528 CT genotype and MCI (OR=0.36, P=0.002), and the PLK2-rs15009 CC and GG genotypes and CC genotype at PLK2-rs702723 with OR ranging from 0.40 to 0.57 on AD. These data suggest that TT or CT genotypes at CAMK2A-rs3756577 is associated with risk reduction for AD and MCI ranging from 2 to nearly 8 times. Our data suggest a possible relation between certain reelin signaling pathway genotypes and cognitive impairment related to AD.

TLR2 and TLR4 Gene Polymorphisms and Atopic Dermatitis in Italian Children: A Multicenter Study

BACKGROUND Genetic factors have an important role in atopic dermatitis (AD) predisposition. Toll like receptor (TLR) are important mediators between environment and immune system. There are incosnsitent studies about TLSR polymorphisms in AD. OBJECTIVE This study examined whether single nucleotide polimorphisms (SNPs) in the genes for TLR2 and TLR4 could be associated with the AD phenotypes and with its clinical severity in a large group of Italian children. METHODS 187 children with Ad and 150 healthy children were recruited. AD severity was assessed by SCORAD. TLR2 (A-16934T and R753Q polymorphisms) and TLR4 (D299G and T399I SNPs) were genotyped by PCR-RFLP. RESULTS The frequency of the R753Q was significantly higher in AD children (16.0 percent) compared with controls (6.0 percent, P =0.004; OR2.99, 95 percent CI 1.39-6.41; RR 1.46, 95 percent CI 1.14-1.69). AD patients a significantly different frequency of the D299G SNP (14.9 percent) in comparison with the controls (6.6 percent, P = 0.01; OR 2.46, 95 percent CI 1.17–5.17; RR 2.24; 95 percent CI 1.15-4.45). CONCLUSION Children with AD may have a distinct genotype and the TLR-2 R753Q SNP was prevalent in a subset of patients with AD characterized by a more severe clinical picture.

A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty-five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047). The enrichment of LRP4 TT genotype in RS was confirmed in an independent series (n = 44) used for validation purposes. The LRP4 protein was expressed in CLL (n =66). Bioinformatic analysis scored LRP4 rs2306029 as a variant with possible deleterious and damaging variant of LRP4. LRP4 genotyping may help the recognition of patients with increased risk of RS at the time of CLL diagnosis.

Sistematic Analysis of ABO Gene in A3 and A3B Individuals Reveals New ABO Variants.

Abstract BACKGROUND: In addition to the common ABO phenotypes, numerous phenotypes with a weak expression of the A or B antigens on red blood cells have been found. DNA genotyping on A3 e A3B subgroups has been performed in small number of samples, mainly in family studies. To date, seven ABO alleles have been associated to A3 and A3B subgroups (ABO*A301 to ABO*A307) revealing molecular heterogeneity. Our purpose was to study molecular events on exon 7 of ABO gene in 100 A3 and A3 B blood donors samples. STUDY DESIGN AND METHODS: ABO serologic analyses of 12,283 blood donors of blood groups A and AB allowed the detection of 13 A3 and 87 A3B samples. Initially, DNA amplification was performed using sequence specific polymerase chain reaction (PCR-SSP) to identify 467C&gt;T, 829G&gt;A, 871G&gt;A and 1060delC polimorphisms of exon 7 of ABO gene, followed by direct DNA sequencing. RESULTS: New ABO variants were detected in 5/13 (38.5%) of A3 and in 38/87 (43.7%) of A3B samples. ABO*A302/ABO*A301 genotype was found in 30.7% A3 and, ABO*A302/ABO*B104 in 17.1% of A3B samples. The 871G&gt;A mutation previously reported only in A3B individuals was found in 9 blood samples tested as A3 in our study. For the first time, mutations between 441–450 nucleotides of exon 7 of ABO gene was detected in 39 samples (single nucleotide polimorphisms and deletions) of A3 and A3B subgroups. CONCLUSION: This is the first large molecular study of A3 and A3B samples. Sistematic analysis of A3 and A3B samples reveals new ABO variants caused by different molecular events. Mutations between 441 and 450 nt. of exon 7 are critical for transferase A expression in individuals typed as A3 and A3B.

Pathogen Variability. A Genomic Signal Approach

The conversion of genomic symbolic sequences into digital signals has been applied for the analysis pathogen variability. Results are given on the variability of Human Immunodeficiency Virus, type 1, subtype F, isolated in Romania, and of the type A avian influenza virus H5N1, for which sequences have been downloaded from GenBank [1]. Nucleotide sequence analysis is corroborated with techniques based on the genomic signal approach to detect pathogen resistance to antiretroviral treatment. In the case of protease (PR) inhibitors, it is found that the treatment induces single nucleotide polimorphisms (SNPs) in specific sites. For moderate resistance, the changes affect the PR enzyme only at the level of the protein, whereas for multiple drug resistance, the RNA gene secondary structure also changes.