scholarly journals Thiopurine S-methyltransferase genetic polymorphisms in adult patients with inflammatory bowel diseases in the Latvian population

2020 ◽  
Vol 13 ◽  
pp. 175628482093742
Author(s):  
Polina Zalizko ◽  
Juris Stefanovics ◽  
Jelizaveta Sokolovska ◽  
Natalia Paramonova ◽  
Evija Klavina ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Fragment Length Polymorphism ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Allelic Variants ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Tpmt Gene ◽  
European Populations

Background: Thiopurine methyltransferase (TPMT) plays a significant role in the metabolism of thiopurines, and, for patients with inflammatory bowel disease (IBD), it is useful to perform TPMT genotyping prior to azathioprine (AZA) treatment. In this study, we determined TPMT gene polymorphisms in a cohort of IBD patients in Latvia. Methods: DNA samples were obtained from 244 IBD patients, and qPCR was performed for detection of rs1800462, rs1800460, and rs1142345 single-nucleotide polymorphisms (SNPs). Three common, non-functional TPMT alleles ( TPMT*2, *3B, and *3C) were identified (women, 51%; men, 49%). TPMT*2, *3A, *3B, and *3C allelic variants detected using qPCR were consistent with restriction fragment length polymorphism (RFLP) data. Results: Among patients, 78% had ulcerative colitis and 22% had Crohn’s disease, with 93.9% of the former carrying a wild-type homozygous TPMT*1/*1 genotype and 6.1% carrying heterozygous genotypes. The most frequent polymorphisms were TPMT*1/*3A (5.3%: two variants: TPMT*3B and TPMT*3C), TPMT*1/*3C (0.4%), and TPMT*1/*2 (0.4%). None of the patients carried a TPMT*3B polymorphism and no patients were homozygous for any mutation. Conclusion: This is the first study to identify TPMT gene polymorphisms in adult IBD patients in Latvia. The results indicate that the frequency of common TPMT alleles is similar to that of other European populations.

scholarly journals Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

2021 ◽  
Vol 22 (4) ◽  
pp. 1832
Author(s):  
Eugene Metakovsky ◽  
Laura Pascual ◽  
Patrizia Vaccino ◽  
Viktor Melnik ◽  
Marta Rodriguez-Quijano ◽  
...  
Keyword(s):  
Common Wheat ◽  
Dna Sequences ◽  
Fragment Length Polymorphism ◽  
Snp Markers ◽  
Group Iv ◽  
Nucleotide Polymorphisms ◽  
High Genetic Diversity ◽  
Single Nucleotide ◽  
Allelic Variants ◽  
B Genome

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.

scholarly journals Toxicity of azathioprine: why and when? analysis of the prevalence of polymorphism in Joinville, SC, Brazil

2012 ◽  
Vol 49 (2) ◽  
pp. 130-134 ◽  
Author(s):  
Gabriela Roncone Gastal ◽  
Simone Moreira ◽  
Caroline Furtado Noble ◽  
Leslie Ecker Ferreira ◽  
Paulo Henrique Condeixa de França ◽  
...  
Keyword(s):  
Blood Donors ◽  
Thiopurine Methyltransferase ◽  
Normal Allele ◽  
Wild Type ◽  
Drug Induced ◽  
Acute Leukemias ◽  
Allelic Variants ◽  
Risk Of Death ◽  
Inflammatory Bowel ◽  
Tpmt Gene

CONTEXT: The use of thiopurine drugs such as azathioprine and 6-mercaptopurine has become quite common in the treatment of inflammatory bowel disease, transplantation and acute leukemias. Despite their effectiveness, these drugs are capable of causing drug-induced toxicity with the risk of death by myelosuppression. It is now known that these complications occur because of genetic polymorphisms of the thiopurinemethyltransferase (TPMT) enzyme, responsible for its metabolism. OBJECTIVE: To assess the prevalence of thiopurine methyltransferase polymorphisms in the population of Joinville, SC, Brazil. METHODS: We analyzed the frequency of four main allelic variants of the TPMT gene in 199 blood donors from Joinville, from February to April 2010. RESULTS: The normal allele ("wild-type") was found in 93.9% of subjects studied. TPMT variants were detected in 12 subjects (6.03%). CONCLUSIONS: From this study, it was estimated at 6% the risk of toxicity by the administration of azathioprine and 6-mercaptopurine to patients in Joinville.

scholarly journals Association of Three Polymorphisms rs11614913, rs2910146, and rs3746444 in miRNA-196a2, miRNA-146a, and miRNA-499 with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Liu ◽  
Lingxin Xiong ◽  
Yan Zhou ◽  
Bingzhen Zheng ◽  
Tongjun Liu ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Meta Analysis ◽  
Case Control ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies ◽  
Single Nucleotide ◽  
Precise Estimation ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Hereditary Susceptibility

Background. It has been found that single-nucleotide polymorphisms (SNPs) of microRNA might be involved in the development of inflammatory bowel diseases (IBDs). However, the related retrospective research has not been reported. In this work, we performed a meta-analysis to derive a more precise estimation of the associated relationship. Methods. We searched the studies on the association of SNPs of microRNA with the hereditary susceptibility of IBD in PubMed and Embase; eligible research was selected by screening the abstract and full text. The meta-analysis was performed based on the statistical software Stata 14.0, and besides, the odds ratio and 95% confidence interval were calculated to evaluate the strength of the association. Results. 159 papers were acquired from the PubMed and Embase databases, and five eligible articles containing nine case-control studies were selected. In the study, we first found that the association between miRNA-196a2 rs11614913 and IBD was insignificant. Then, the susceptibility of miRNA-146a rs2910146 to IBD increased significantly in allelic comparison, homozygote model, heterozygote model, and dominant model. Moreover, a positive relationship between miRNA-499 rs3746444 and IBD was identified in the homozygote model. Conclusion. Our findings demonstrated that miRNA-146a rs2910146 (G>C) polymorphism was associated with the susceptibility to IBD and miRNA-196a2 rs11614913 (T>C) and miRNA-499 rs3746444 (A>G) did not reveal an obvious relationship with the IBD susceptibility.

scholarly journals Lactose Malabsorption and Lactose Intolerance in Children with Inflammatory Bowel Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Martyna Jasielska ◽  
Urszula Grzybowska-Chlebowczyk
Keyword(s):  
Lactose Intolerance ◽  
Bone Mineralization ◽  
Nucleotide Polymorphisms ◽  
Functional Abdominal Pain ◽  
Hydrogen Breath Test ◽  
Adult Type ◽  
Single Nucleotide ◽  
Lactose Malabsorption ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background. Insufficient vitamin D and calcium intake associated with the restricted intake of milk and dairy products can lead to poor health outcomes like malnutrition and abnormal bone mineralization. The aim of the study was to estimate the prevalence of primary and secondary lactose intolerance in children with IBD. Methods. The study included 107 patients (mean age 14.07±3.58 years; 46.7% boys) which includes 43 patients with Crohn’s disease (CD), 31 with ulcerative colitis (UC), and 33 children with functional abdominal pain (AP-FGID). We analysed the result of the hydrogen breath test with lactose loading, two single nucleotide polymorphisms of the LCT gene (LCT-13910CC and LCT-22018GG). The results were analysed with MedCalc Statistical Software. Results. Adult-type hypolactasia (ATH) was found in 31% of patients with IBD and 42.4% of AP-FGID (p=0.2). Lactose malabsorption (LM) was found in 27.9% of patients with CD, in 22.6% with UC, and in 24.2% with AP-FGID (p=0.8). Lactose intolerance (LI) was diagnosed in a similar percentage of patients in each group (p=0.9). Secondary LI in IBD patients does not depend on the location, duration, and activity of the disease and the number of relapses (p>0.05). The median time of lactose-free diet in CD was 10 months and in CU 24 months. Conclusions. The incidence of LI, LM, and ATH does not differ among children with IBD from the population.

scholarly journals IMMUNOLOGICAL AND GENETIC FEATURES OF PATHOGENETIC ASSOCIATION BETWEEN PSORIASIS AND COLONIC DYSBIOSIS.

2019 ◽  
Author(s):  
A. A. Goncharov ◽  
O. V. Dolgikh
Keyword(s):  
Bacterial Community ◽  
Single Nucleotide Polymorphisms ◽  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Bacterial Species ◽  
Intestinal Barrier ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Psoriasis is a multifactorial systemic immune-associated disease. It is assumed that colonic dysbiosis may contribute to its development. In this review we provide data on colonic dysbiosis in induction and progression of psoriatic inflammation assessing a role for bacterial species: Akkermansia muciniphila, Faecalibacterium prausnitzii and Escherichia coli. On one hand, these bacterial species indicate at state of bacterial community in dysbiosis. On the other hand, they are functionally associated with triggering a chain of events consisting in inducing impaired intestinal barrier transforming into chronic inflammation in colonic mucosa and systemic inflammation. Such scenario leads to altered systemic reactivity of innate and adaptive immune cells, impaired function of regulatory immune cells, which leads to an expansion of the autoreactive skin T-cells and induction of psoriatic inflammation due to molecular mimicry between persistent Streptococcus pyogenes and cutaneous antigens. The psoriatic process is envisioned as a comorbidity with inflammatory bowel diseases. Since dysbiotic changes in psoriasis and inflammatory bowel diseases (e. g. Crohn's disease) display similar features, these diseases might potentially proceed via a similar pathogenetic chain resulting from dysbiotic changes in intestinal microbiota to impaired intestinal barrier, chronic systemic inflammation and altered anti-inflammatory immune arm. Therefore, the data on pathogenetic pathways of diseases comorbid with psoriasis are able to uncover yet-unknown pathogenetic components for the latter. Psoriasis as a genetically-determined disease is currently believed to be associated with single nucleotide polymorphisms (SNP) in more than four hundred genes. A role for diverse SNPs in candidate genes involved in psoriasis pathogenetic chain at antigen processing and presentation, migration of immune cells, ligation and production of pro-inflammatory cytokines is discussed. Crohn's disease is associated with single nucleotide polymorphisms of genes encoding intestinal barrier proteins potentially underlying its functional deficiency. In connection with comorbidity and similarity between microbiota-associated pathogenetic psoriasis chain and inflammatory bowel diseases, it is possible to assume that such SNPs accounting for genetic defects in the intestinal barrier are manifested as dysbiotic changes in colonic bacterial community and contribute to progression not only of inflammatory bowel diseases, but psoriasis as well.

scholarly journals Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 441 ◽  
Author(s):  
Ribaldone ◽  
Adriani ◽  
Caviglia ◽  
Nicolò ◽  
Agnesod ◽  
...  
Keyword(s):  
Adverse Events ◽  
Therapeutic Option ◽  
Gene Mutations ◽  
Homozygous Mutation ◽  
Allelic Variants ◽  
Entire Cohort ◽  
Significant Difference ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Tpmt Gene

Background and Objectives: In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a possible correlation between genetic variability of the enzyme thiopurine S-methyltransferase (TPMT) and the development of toxicity to azathioprine. Materials and Methods: A retrospective, single center, blind, case-control study was conducted on 200 IBD patients, of whom 60 cases suspended azathioprine due to toxicity (leukopenia, pancreatitis, hepatitis, and nausea or vomiting), and 140 controls continued treatment with the drug without adverse events. Results: In the entire cohort, only 8 cases of heterozygous mutations of TPMT were observed, corresponding to 4% mutated haplotype rate, much lower than that reported in literature (close to 10%). No homozygous mutation was found. Regarding the TPMT allelic variants, we did not find any statistically significant difference between patients who tolerated azathioprine and those who suffered from adverse events. (OR = 0.77, 95% CI = 0.08–7.72; p = 0.82). Conclusions: According to our study, in IBD patients, the search for TPMT gene mutations before starting treatment with azathioprine is not helpful in predicting the occurrence of adverse events. Importantly, patients with allelic variants should not be denied the therapeutic option of azathioprine, as they may tolerate this drug.

Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

2021 ◽  
pp. 112067212110026
Author(s):  
Pablo Gili ◽  
Leyre Lloreda Martín ◽  
José-Carlos Martín-Rodrigo ◽  
Naon Kim-Yeon ◽  
Laura Modamio-Gardeta ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Gene Polymorphisms ◽  
Age Related Macular Degeneration ◽  
Spanish Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

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