scholarly journals Pharmacogenetic approach to methotrexate-related toxicity prediction in psoriasis

2021 ◽  
Vol 24 (2) ◽  
pp. 119-132
Author(s):  
Alexey А. Kubanov ◽  
Anastasiia V. Asoskova ◽  
Dmitriy A. Sychev
Keyword(s):  
Interindividual Variability ◽  
Current Knowledge ◽  
Nucleotide Polymorphisms ◽  
Therapy Discontinuation ◽  
Single Nucleotide ◽  
Peripheral Tissues ◽  
Toxicity Risk ◽  
Genes Encoding ◽  
Treatment Data ◽  
Treatment Personalization

Methotrexate is a highly effective for psoriasis, but the use of methotrexate may be limited by its adverse effects. Approximately 1030% of patients treated with methotrexate experience adverse drug reactions, leading to the therapy discontinuation. Patient genetics can play a significant role in the interindividual variability of drug response. There is a growing body of literature on allelic variants of various genes that are assosiated with methotrexate toxicity. Pharmacogenetic studies may establish how patients genotype affect the safety of methotrexate. Treatment Data shows that to predict the risk of methotrexate-induced toxicity it is necessary to take into account the interindividual variability in methotrexate pharmacokinetics, which may be determined by the presence of single-nucleotide polymorphisms of genes encoding methotrexate carrier proteins and enzymes of its biotransformation. The activity of transporter proteins affects the drugs in the blood plasma and peripheral tissues, thereby determining its toxicity. The review was aimed is to summarize the current knowledge on pharmacogenetic polymorphisms that may affect the variability of methotrexate-related toxicity. Evaluation of such promising candidates for predictors of methotrexate-related toxicity risk could be used in psoriasis treatment personalization.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

scholarly journals Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aner Mesic ◽  
Marija Rogar ◽  
Petra Hudler ◽  
Nurija Bilalovic ◽  
Izet Eminovic ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
In Silico ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mitotic Kinases ◽  
Genes Encoding ◽  
Silico Analysis ◽  
Control Study

Abstract Background Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). Methods Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. Results The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. Conclusions Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings.

scholarly journals A Locus on Mouse Chromosome 2 Is Involved in Susceptibility to Congenital Hypothyroidism and Contains an Essential Gene Expressed in Thyroid

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1948-1958 ◽  
Author(s):  
Elena Amendola ◽  
Remo Sanges ◽  
Antonella Galvan ◽  
Nina Dathan ◽  
Giacomo Manenti ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Chromosomal Region ◽  
Essential Gene ◽  
Chromosome 2 ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genes Encoding ◽  
Mouse Chromosome 2 ◽  
Essential Function

We report here the mapping of a chromosomal region responsible for strain-specific development of congenital hypothyroidism in mice heterozygous for null mutations in genes encoding Nkx2-1/Titf1 and Pax8. The two strains showing a differential predisposition to congenital hypothyroidism contain several single-nucleotide polymorphisms in this locus, one of which leads to a nonsynonymous amino acid change in a highly conserved region of Dnajc17, a member of the type III heat-shock protein-40 (Hsp40) family. We demonstrate that Dnajc17 is highly expressed in the thyroid bud and had an essential function in development, suggesting an important role of this protein in organogenesis and/or function of the thyroid gland.

scholarly journals Variation of genes encoding KAT1, AADAT and IDO1 as a potential risk of depression development

2018 ◽  
Vol 52 ◽  
pp. 95-103 ◽  
Author(s):  
Paulina Wigner ◽  
Piotr Czarny ◽  
Ewelina Synowiec ◽  
Michał Bijak ◽  
Monika Talarowska ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Nucleotide Polymorphisms ◽  
Male Population ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Genes Encoding ◽  
Numerous Data ◽  
Tryptophan Catabolites ◽  
Hydroxyanthranilic Acid ◽  
The Relationship

AbstractBackground:Numerous data suggests that the disorders of tryptophan catabolites (TRYCATs) pathway, including a decreased level of tryptophan or evaluated concentration of harmful TRYCATs −kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, 3-hydroxytryptophan − may cause the occurrence of DD symptoms. In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls. We genotyped, by using TaqMan probes, four polymorphisms: c.*456G > A of KAT1 (rs10988134), c.975-7T > C of AADAT (rs1480544), c.-1849C > A (rs3824259) and c.-1493G > C(rs10089084)of IDO1. We found that only the A/A genotype of c.*456G > A − KAT1 (rs10988134) increased the risk of depression occurrence. Interestingly, when we stratified the study group according to gender, this relationship was present only in male population. However, a gene–gene analysis revealed a link between the T/T-C/C genotype of c.975-7T > C − AADAT (rs1480544)or c.-1493G > C − IDO1 (rs10089084) and C/C-C/A genotype of c.975-7T > C − AADAT (rs1480544)and c. −1849C > A − IDO1 (rs3824259) and the disease. Moreover, we found, that the c.975-7T > C − AADAT and c. *456G > A KAT1 (rs10988134) polymorphisms may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. Concluding, our results confirm the hypothesis formulated in our recently published article that the SNPs of genes involved in TRYCATs pathway may modulate the risk of depression. This provides some further evidence that the pathway plays the crucial role in development of the disease.

scholarly journals FUT2, Secretor Status and FUT3 Polymorphisms of Children with Acute Diarrhea Infected with Rotavirus and Norovirus in Brazil

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1084
Author(s):  
Marco André Loureiro Tonini ◽  
Débora Maria Pires Gonçalves Barreira ◽  
Luciana Bueno de Freitas Santolin ◽  
Lays Paula Bondi Volpini ◽  
José Paulo Gagliardi Leite ◽  
...  
Keyword(s):  
Acute Diarrhea ◽  
Current Knowledge ◽  
Host Susceptibility ◽  
High Rate ◽  
Southeastern Brazil ◽  
Blood Group Antigens ◽  
Nucleotide Polymorphisms ◽  
Symptomatic Infection ◽  
Single Nucleotide ◽  
Secretor Status

Host susceptibility according to human histo-blood group antigens (HBGAs) is widely known for norovirus infection, but is less described for rotavirus. Due to the variable HBGA polymorphism among populations, we aimed to evaluate the association between HBGA phenotypes (ABH, Lewis and secretor status) and susceptibility to rotavirus and norovirus symptomatic infection, and the polymorphisms of FUT2 and FUT3, of children from southeastern Brazil. Paired fecal-buccal specimens from 272 children with acute diarrhea were used to determine rotavirus/norovirus genotypes and HBGAs phenotypes/genotypes, respectively. Altogether, 100 (36.8%) children were infected with rotavirus and norovirus. The rotavirus P[8] genotype predominates (85.7%). Most of the noroviruses (93.8%) belonged to genogroup II (GII). GII.4 Sydney represented 76% (35/46) amongst five other genotypes. Rotavirus and noroviruses infected predominantly children with secretor status (97% and 98.5%, respectively). However, fewer rotavirus-infected children were Lewis-negative (8.6%) than the norovirus-infected ones (18.5%). FUT3 single nucleotide polymorphisms (SNP) occurred mostly at the T59G > G508A > T202C > C314T positions. Our results reinforce the current knowledge that secretors are more susceptible to infection by both rotavirus and norovirus than non-secretors. The high rate for Lewis negative (17.1%) and the combination of SNPs, beyond the secretor status, may reflect the highly mixed population in Brazil.

scholarly journals Evaluation of polymorphisms in inflammatory mediator and cellular adhesion genes as risk factors for feline infectious peritonitis

2019 ◽  
Vol 22 (6) ◽  
pp. 564-570 ◽  
Author(s):  
Helen Kedward-Dixon ◽  
Emi N Barker ◽  
Séverine Tasker ◽  
Anja Kipar ◽  
Christopher R Helps
Keyword(s):  
Inflammatory Mediator ◽  
Cellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Nucleotide Polymorphisms ◽  
Necrosis Factor Alpha ◽  
Single Nucleotide ◽  
Feline Infectious Peritonitis ◽  
Genes Encoding ◽  
Factor Alpha ◽  
Necrosis Factor

Objectives Feline infectious peritonitis (FIP) is a high mortality infectious disease. Single nucleotide polymorphisms (SNPs) in the genes encoding interferon gamma ( IFNG), tumour necrosis factor alpha ( TNFA) and dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) have been associated with increased and decreased risk of developing FIP. This study was designed to determine whether these associations were present in a UK population of pedigree cats using samples from cats euthanased with a confirmed diagnosis (FIP, n = 22; non-FIP, n = 10) or clinically healthy cats over 11 years of age (n = 3). Methods DNA was extracted from tissue (n = 32) or blood (n = 3) and PCR performed for regions of IFNG, TNFA and CD209. PCR amplicons were sequenced, each SNP genotype was determined, and genotype/allele frequency for each SNP and FIP status were compared. Results No significant association was found between the genotype and FIP status for any SNP analysed. There was a trend for the heterozygous CT genotype at both IFNG g.401 and IFNG g.408 to be associated with FIP ( P = 0.13), but this genotype was also found in a substantial proportion of non-FIP cats. There was also a trend for the heterozygous CT genotype at IFNG g.428 to be associated with FIP ( P = 0.06), although most cats with FIP had the CC genotype at this locus. No associations were found between any allele at TNFA g.-421, CD209 g.1900, CD209 g.2276, CD209 g.2392 and CD209 g.2713 and FIP. Conclusions and relevance The use of the IFNG, TNFA and CD209 SNPs described to predict the risk of FIP cannot currently be recommended.

scholarly journals Recent Transposition of an LTR-Retrotransposon in the Gene Coding for S Receptor Kinase is Responsible for a Novel Self-Compatible Phenotype of Radish (Raphanus Sativus L.)

2021 ◽  
Author(s):  
So-Hyeon Bong ◽  
Ganghee Cho ◽  
Dong-Seon Kim ◽  
Sunggil Kim
Keyword(s):  
Raphanus Sativus ◽  
Phylogenetic Analyses ◽  
Ltr Retrotransposon ◽  
Nucleotide Polymorphisms ◽  
Receptor Kinase ◽  
Coding Region ◽  
Single Nucleotide ◽  
Breeding Lines ◽  
Gene Coding ◽  
Genes Encoding

Abstract Self-incompatibility (SI) responses of radish (Raphanus sativus L.) are determined by two tightly linked genes encoding an S receptor kinase (SRK) and an S-locus cysteine-rich protein/S locus protein 11 (SCR/SP11), respectively. A radish showing an almost self-compatible (SC) phenotype was identified in this study. Inheritance patterns showed that this SC phenotype was dominant over an SI phenotype. In addition, this SC phenotype co-segregated with an S haplotype in an F2 population. This SC radish contained an RsS-26 haplotype in which duplicate SRK-like genes were previously identified. Full-length sequences of two SRK-like genes of 18,133-bp and 6,200-bp in length were obtained from radish with the RsS-26 haplotype (designated as RsSRK-26-1 and RsSRK-26-2, respectively). Duplicate SCR/SP11-like genes were also identified in the radish with the RsS-26 haplotype. Phylogenetic analyses indicated that both duplicate SRK-like and SCR/SP11-like genes were closely related to other known SRK and SCR/SP11 genes, respectively. No critical mutation was found in the coding region of SRK-like or SCR/SP11-like gene. However, a 4,146-bp intact LTR-retrotransposon was identified in the third intron of RsSRK-26-1 of the SC radish. Interestingly, this LTR-retrotransposon was not detected in three other breeding lines containing the same RsS-26 haplotype. Except for this LTR-retrotransposon, only two single nucleotide polymorphisms (SNPs) were identified in intronic regions between normal and mutant RsSRK-26-1 alleles. While normal transcription was observed for radish showing RsSRK-26-1 and SI phenotypes in these three breeding lines, no transcript of RsSRK-26-1 was detected in the SC radish, suggesting that recent transposition of an LTR-retrotransposon in the RsSRK-26-1 gene might be responsible for the SC phenotype of radish.

scholarly journals Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes—A Narrative Review of the Case of Vitamins

2020 ◽  
Vol 7 ◽  
Author(s):  
Aikaterini Niforou ◽  
Valentini Konstantinidou ◽  
Androniki Naska
Keyword(s):  
Vitamin D ◽  
Vitamin C ◽  
Genetic Variants ◽  
Current Knowledge ◽  
Association Studies ◽  
Genetic Variations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Dietary Intakes ◽  
Genes Encoding

Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.

The Association of CYP2D6*4 and POR*28 Polymorphisms on Mirtazapine Plasma Level in Subjects with Major Depressive Disorder and Anxiety Disorders

2020 ◽  
Vol 23 (10) ◽  
pp. 1032-1040
Author(s):  
Fezile Ozdemir ◽  
Emrah Dural ◽  
Nilay Sedes Baskak ◽  
Yağmur Kır ◽  
Bora Baskak ◽  
...  
Keyword(s):  
Plasma Level ◽  
Plasma Levels ◽  
Psychiatric Patients ◽  
Nucleotide Polymorphisms ◽  
Major Depressive ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Study Population ◽  
Polymerase Chain

Aims and Objective: The plasma level of mirtazapine (MIR) varies between individuals primarily depending on the differences in metabolism during pharmacotherapy. CYP2D6 takes the role as a major enzyme in MIR metabolism and POR enzyme donates an electron to CYP2D6 for its activity. Single nucleotide polymorphisms in the genes encoding pharmacokinetic enzymes may cause changes in enzyme activity, leading to differences in metabolism of the drug. Our aim was to assess the influence of CYP2D6*4 and POR*28 polymorphisms on MIR plasma levels in Turkish psychiatric patients. Materials and Methods: The association between genetic variations and plasma level of MIR was investigated on 54 patients. CYP2D6*4 and POR*28 polymorphisms were analysed using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) and plasma MIR levels were measured using HPLC. Results: Allele frequencies of CYP2D6*4 and POR*28 were 0.11 and 0.39, respectively in the study population. The results showed that CYP2D6*4 allele carriers have higher C/D MIR levels while POR*28 allele carriers have lower C/D MIR levels. Combined genotype analyses also revealed that individuals with CYP2D6*1/*1 - POR*28/*28 genotype have a statistically lower C/D MIR level (0.95 ng/ml/dose) when compared with individuals with CYP2D6*1/*1 - POR*1/*1 genotype (1.52 ng/ml/dose). Conclusion: Our results indicate that CYP2D6*4 and POR*28 polymorphisms may have a potential in the explanation of differences in plasma levels in MIR treated psychiatric patients. A combination of these variations may be beneficial in increasing drug response and decreasing adverse drug reactions in MIR psychopharmacotherapy.

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