scholarly journals Factors associated with rs1801394 of the methionine synthase reductase gene polymorphism in patients with rheumatoid arthritis

2021 ◽  
Vol 15 (3) ◽  
pp. 15-19
Author(s):  
M. Yu. Krylov ◽  
G. I. Gridneva ◽  
Yu. V. Muravyev

Clinical response to methotrexate (MT) therapy in rheumatoid arthritis (RA) can be predicted on the basis of some single nucleotide polymorphisms (SNPs) of genes, involved in folate metabolism. One of these SNPs is the rs1801394 (A66G) polymorphism of the methionine synthase reductase gene (MTRR). We investigated the association of this polymorphism with the clinical characteristics of RA patients after 6 months of MT therapy. Studies of the relationship between the response to MT therapy and the rs1801394 polymorphism have not been carried out in Russia previously.Objective: to study the possible association of the rs1801394 polymorphism with the clinical characteristics of patients with RA after 6 months of MT therapy.Patients and methods. The study included 60 patients with RA who met the ACR / EULAR criteria (2010) and received≥20 mg MT per week continuously. Based on the EULAR criteria, patients were divided into two groups: group 1 (n=30) with a good (DAS28>1.2) and group 2 (n=30) with an unsatisfactory (DAS28 <1.2) response to MT therapy. Genotyping of the rs1801394 polymorphism was performed by allelic discrimination using real-time polymerase chain reaction.Results and discussion. The frequency distribution of the A66G polymorphism genotypes in both groups was similar, however, in the 2nd group with an unsatisfactory response, there was a tendency towards a higher frequency of the mutant GG genotype (p=0.067). An association of the A66G polymorphism with gender and disease duration was found. In group 1, the AG genotype was more often detected in men than in women (p=0.017). In group 2, the AG genotype was also more common in men (p=0.075). In addition, in this group, carriers of the G allele (genotypes AG and GG) had a longer duration of the disease than carriers of the AA genotype (p=0.003 and p=0.005, respectively).Conclusion. In the present study, the relationship of the studied polymorphism rs1801394 of the MTRR gene with gender and duration of RA disease was established.

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Thushyanthan Guruparan ◽  
Matthew Hutchinson ◽  
Rhys Hayward ◽  
Henry Penn ◽  
Parul Kalia

Abstract Background/Aims  The effects of antinuclear antibodies (ANA) in rheumatoid arthritis (RA) are not fully characterised. Studies investigating the effect of ANA on disease activity in RA have yielded mixed results. The presence of ANA has been correlated with higher levels of CRP and joint inflammation in RA. Evidence suggests that ANA positivity at baseline may predict poor response to both traditional disease modifying agents and biologic therapy. ANA may also be associated with higher incidences of ocular disease, Felty’s syndrome, vasculitis and subjective pain in RA patients. On the other hand, other studies showed a lack of correlation between ANA status and joint inflammation in RA. Our study investigates the relationship between ANA positivity and joint erosions in rheumatoid patients. Methods  This is a cross-sectional study of patients attending the early arthritis clinic at Northwick Park Hospital in London over a five year period (2014-2019). A total of 631 patients were identified of whom 261 had RA. We collected data on the age, gender, ANA positivity, the presence of anti-CCP (anti cyclic-citrullinated peptide) antibodies and rheumatoid factor (RF) at presentation as well as the presence of erosive disease on radiological reports of hand X-rays. Positive ANA was defined as having a titre of 1:80 or greater. Patients with missing ANA result or hand X-ray reports were excluded, leaving 228 patients. Two-tailed Chi-square tests for categorical data and two-tailed student’s t-tests for continuous data were performed to determine the statistical significance of comparisons made between the ANA positive and negative groups. Results  Of the 228 patients, 49 (21.5%) were male and 179 (78.5%) were female. The mean age was 58 years. 84 (36.8%) patients were ANA positive (group 1) and 144 (63.2%) were ANA negative (group 2). In group 1, 23/84 (27.4%) patients had erosive disease. In group 2, erosions were found in 25/144 patients (17.4%). This difference was not statistically significant (p = 0.073). The number of patients who were RF positive in groups 1 and 2 were 79.5% and 73.6% respectively (p = 0.317); 75/84 (89.3%) patients in group 1 and 113/143 (79.0%) in group 2 were anti-CCP antibody positive (p = 0.048). The means of the age of patients were 53 and 62 years in group 1 and group 2 respectively (p &lt; 0.0001); the ANA positive group was significantly younger. The male:female ratio was 13:71 in group 1 and 36:108 in group 2 (p = 0.091). Conclusion  Our study showed no significant association between ANA status and erosive disease in RA, although a greater proportion of patients had erosions in the ANA positive group. Larger observational studies may better study this relationship. Disclosure  T. Guruparan: None. M. Hutchinson: None. R. Hayward: None. H. Penn: None. P. Kalia: None.


2021 ◽  
pp. 1-7
Author(s):  
Emre Erdem ◽  
Ahmet Karatas ◽  
Tevfik Ecder

<b><i>Introduction:</i></b> The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. <b><i>Methods:</i></b> A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin &#x3c;800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin &#x3e;1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. <b><i>Results:</i></b> Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, <i>p</i> = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; <i>p</i> = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; <i>p</i> = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; <i>p</i> = 0.063). <b><i>Conclusion:</i></b> Time-averaged serum ferritin levels &#x3e;1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1008.2-1008
Author(s):  
L. Fang ◽  
Z. Lin ◽  
Z. Liao ◽  
O. Jin ◽  
Y. Pan ◽  
...  

Background:Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent rheumatoid arthritis (RA) and HBV infection were available by now.Objectives:To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with RA.Methods:In this 52 weeks observation, HBsAg carriers with active RA (DAS28>5.1) despite failed combined treatment with MTX and other non-biological DMARDs were enrolled. Patients must have normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily) and concomitant MTX (10-12.5mg/w). Entecavir was prescribed preventively for patients who had a baseline HBV load >2000 copy/ml (group 1), and Lamivudin for patients with HBV load ≤ 2000 copy/ml (group 2). Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion.Results:Thirteen patients (10 female) were recruited. Nine patients had a baseline viral load >2000 copy/ml (group 1, with preventive Entecavir), and the other 4 patients had a viral load ≤ 2000 copy/ml (group 2, with preventive Lamivudin). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib.No reactivation of hepatitis B was observed in patients from group 1. One patients (female, 54 years old) from group 2 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16. An elevated viral load (4.9e6 copies/ml, baseline 1.4e3) and a HBV YMDD mutant was also found. The tofacitinib treatment continued. After prescription of Adefovir (combined with the pre-existing Lamivudin), both liver enzyme and viral load decreased to normal range in 8 weeks and remained normal throughout the study.Conclusion:An aggressive Tofacitinib + MTX therapy may be a safe option for HBsAg carriers with cs-DMARDs refractory RA. More active and effective prophylaxis strategy may be recommended to reduce the risk of HBV reactivation during the treatment.References:[1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2.Disclosure of Interests: :None declared


Author(s):  
Yangseop Noh ◽  
Ji-Eun Choi ◽  
Kyung Eun Lee ◽  
Seung-Kyu Chung ◽  
Sang Duk Hong ◽  
...  

Background and Objectives One of the most common surgical procedures in children is adenoidectomy, but the causes of adenoid hypertrophy are not fully understood. Some studies have found that allergies can be a risk factor for adenoid hypertrophy, asthma being one of these allergic diseases. This study aimed to investigate the relationship between adenoid size and asthma in a group of children.Subjects and Method This study reviewed a total of 2063 pediatric patients with or without atopy and asthma who visited the Otorhinolaryngology and Pediatric unit at a tertiary medical center from January 2011 to June 2016. We classified these patients into 4 groups according to the presence of asthma or atopy and randomly selected 100 patients from each group (to a total of 400 pts): group 1 (asthma-, atopy-); group 2 (asthma-, atopy+); group 3 (asthma+, atopy-) and group 4 (asthma+, atopy+). The presence of allergic sensitization (atopy) was evaluated by CAP test and total IgE. Asthma was diagnosed according to the diagnosis criteria in the Korean guideline for asthma. Adenoid size was evaluated with the adenoidal-nasopharyngeal ratio (A/N ratio) by the adenoid view.Results The four groups did not differ from each other significantly in age or sex. There was a negative correlation between adenoid size and atopic and asthmatic condition. Group 1 had a significantly larger A/N ratio than the other groups (group 1=0.534±0.138; group 2=0.469± 0.140; group 3=0.476±0.135; group 4=0.482±0.128, <i>p</i><0.05). However, group 4 showed nearly identical results to groups 2 and 3, despite the combination of asthma and atopy in group 4.Conclusion Large adenoids were negatively associated with atopy and asthma. This finding may be explained by a decrease in adenoid stimulation by nasal obstruction and a difference in the immune system, including allergic immune reactions. Further studies are needed.


2000 ◽  
Vol 38 (2) ◽  
pp. 669-676 ◽  
Author(s):  
Hanna Soini ◽  
Xi Pan ◽  
Amol Amin ◽  
Edward A. Graviss ◽  
Anees Siddiqui ◽  
...  

Mycobacterium tuberculosis isolates (n= 1,429) from 1,283 patients collected as part of an ongoing population-based tuberculosis epidemiology study in Houston, Texas, were analyzed by spoligotyping and IS6110 profiling. The isolates were also assigned to one of three major genetic groups on the basis of nucleotide polymorphisms located at codons 463 and 95 in the genes (katG and gyrA) encoding catalase-peroxidase and the A subunit of DNA gyrase, respectively. A total of 225 spoligotypes were identified in the 1,429 isolates. There were 54 spoligotypes identified among 713 isolates (n= 623 patients) assigned to 73 IS6110 clusters. In addition, among 716 isolates (n = 660 patients) with unique IS6110 profiles, 200 spoligotypes were identified. No changes were observed either in the IS6110 profile or in the spoligotype for the 281 isolates collected sequentially from 133 patients. Five instances in which isolates with slightly different spoligotypes had the same IS6110 profile were identified, suggesting that in rare cases isolates with different spoligotypes can be clonally related. Spoligotypes correlated extremely well with major genetic group designations. Only three very similar spoligotypes were shared by isolates from genetic groups 2 and 3, and none was shared by group 1 and group 2 organisms or by group 1 and group 3 organisms. All organisms belonging to genetic groups 2 and 3 failed to hybridize with spacer probes 33 to 36. Taken together, the results support the existence of three distinct genetic groups of M. tuberculosis organisms and provide new information about the relationship between IS6110 profiles, spoligotypes, and major genetic groups of M. tuberculosis.


1993 ◽  
Vol 264 (4) ◽  
pp. G596-G600 ◽  
Author(s):  
M. F. Stolk ◽  
K. J. van Erpecum ◽  
A. J. Smout ◽  
L. M. Akkermans ◽  
J. B. Jansen ◽  
...  

We examined the relationship of interdigestive gallbladder emptying with the different phases of the migrating motor complex (MMC) and with plasma levels of cholecystokinin (CCK) and motilin. In 10 volunteers 20 cycles of the MMC were recorded. In 11 cycles phase III occurred in antrum and duodenum (group 1). In nine cycles phase III was observed only in duodenum (group 2). In group 1 gallbladder emptying started at 30% of total cycle length and continued until the end of the cycle. Maximal gallbladder emptying was 33.3 +/- 3.3% (SE). In group 2 gallbladder emptying also started at 30% of total cycle length but ended at 60%. Maximal gallbladder emptying in this group was 24.3 +/- 3.1% (P < 0.05). Motilin levels were higher in group 1 than in group 2 during phase IIB (240.1 +/- 28.5 and 142.1 +/- 30.9 pg/ml, respectively, P < 0.05) and during phase III (210.8 +/- 24.3 and 93.5 +/- 12.5 pg/ml, respectively, P < 0.05). We conclude that: 1) phase III activities starting in the antrum are preceded by greater and prolonged gallbladder emptying, higher motilin levels, and higher intraduodenal bile acid concentrations than phase III activities starting in the duodenum and 2) no relationship between interdigestive gallbladder motility and CCK levels could be demonstrated.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tzyy-Chang Ho ◽  
Allen Yi-Lun Ho ◽  
Muh-Shy Chen

Abstract Differences in the pathogenesis and clinical characteristics between lamellar macular hole (LMH) with and without LMH-associated epiretinal proliferation (LHEP) can have surgical implications. This study investigated the effects of treating LHEP by foveolar internal limiting membrane (ILM) non-peeling and epiretinal proliferative (EP) tissue repositioning on visual acuity and foveolar architecture. Consecutive patients with LHEP treated at our institution were enrolled. The eyes were divided into a conventional total ILM peeling group (group 1, n = 11) and a foveolar ILM non-peeling group (group 2, n = 22). In group 2, a doughnut-shaped ILM was peeled, leaving a 400-μm-diameter ILM without elevated margin over the foveola after EP tissue repositioning. The EP tissue was elevated, trimmed, and inverted into the LMH. Postoperatively, the LMH was sealed in all eyes in group 2, with significantly better best-corrected visual acuity (−0.26 vs −0.10 logMAR; p = 0.002). A smaller retinal defect (p = 0.003), a more restored ellipsoid zone (p = 0.002), and a more smooth foveal depression (p < 0.001) were achieved in group 2. Foveolar ILM non-peeling and EP tissue repositioning sealed the LMH, released the tangential traction, and achieved better visual acuity. The presumed foveolar architecture may be reconstructed surgically. LMH with LHEP could have a combined degenerative and tractional mechanism.


2020 ◽  
Vol 8 (6) ◽  
pp. 232596712092793
Author(s):  
Christopher Antonacci ◽  
Thomas R. Atlee ◽  
Peter N. Chalmers ◽  
Christopher Hadley ◽  
Meghan E. Bishop ◽  
...  

Background: Pitching velocity is one of the most important metrics used to evaluate a baseball pitcher’s effectiveness. The relationship between age and pitching velocity after a lighter ball baseball training program has not been determined. Purpose/Hypothesis: The purpose of this study was to examine the relationship between age and pitching velocity after a lighter ball baseball training program. We hypothesized that pitching velocity would significantly increase in all adolescent age groups after a lighter baseball training program, without a significant difference in magnitude of increase based on age. Study Design: Cohort study; Level of evidence, 2. Methods: Baseball pitchers aged 10 to 17 years who completed a 15-week training program focused on pitching mechanics and velocity improvement were included in this study. Pitchers were split into 3 groups based on age (group 1, 10-12 years; group 2, 13-14 years; group 3, 15-17 years), and each group trained independently. Pitch velocity was assessed at 4 time points (sessions 3, 10, 17, and 25). Mean, maximum, and mean change in pitch velocity between sessions were compared by age group. Results: A total of 32 male baseball pitchers were included in the analysis. Mean/maximum velocity increased in all 3 age groups: 3.4/4.8 mph in group 1, 5.3/5.5 mph in group 2, and 5.3/5.2 mph in group 3. While mean percentage change in pitch velocity increased in all 3 age groups (group 1, 6.5%; group 2, 8.3%; group 3, 7.6%), the magnitude of change was not significantly different among age groups. Program session number had a significant effect on mean and maximum velocity, with higher mean and maximum velocity seen at later sessions in the training program ( P = .018). There was no interaction between age and program session within either mean or maximum velocity ( P = .316 and .572, respectively). Conclusion: Age had no significant effect on the magnitude of increase in maximum or mean baseball pitch velocity during a velocity and mechanics training program in adolescent males.


Author(s):  
Isana Silva ◽  
Manoela Ramos ◽  
Lídia Arantes ◽  
André Lengert ◽  
Marco Oliveira ◽  
...  

Methylation levels in tumor-suppressor genes and repetitive sequences have previously been used to study the relationship between environmental air pollution and epigenetic changes related to cancer. In this study, we measured the methylation profiles of the promoter regions CDKN2A, MLH1 and APC and the repetitive sequence LINE-1 in 59 workers exposed to the construction environment and in 49 unexposed workers. We also evaluated the micronuclei frequency and levels of trace elements in the blood of all workers. We evaluated of levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) at the construction site to characterize the environmental exposure. Our findings demonstrated that exposed workers exhibited significantly higher average levels of promoter methylation of CDKN2A, APC, and MLH1 genes and increased hypomethylation of the LINE-1 in comparison to unexposed workers (all p < 0.05). A higher frequency of micronuclei was observed in the exposed group (2 ± 2) compared to the unexposed group (1 ± 1) with p < 0.001. High levels of particulate matter (51–841 μg/m3) and some PAHs were found in samples from the construction environment. In summary, we provide evidence of increased DNA damage and altered DNA methylation of exposed workers, suggesting that genomic approaches to biomonitoring may be an effective way of estimating future cancer risk for construction workers.


2020 ◽  
Vol 16 (28) ◽  
pp. 2219-2233
Author(s):  
Yanliang Bai ◽  
Emmanuel Kwateng Drokow ◽  
Hafiz Abdul Waqas Ahmed ◽  
Juanjuan Song ◽  
Gloria Selorm Akpabla ◽  
...  

Background: The relationship between hematological cancer susceptibility and methionine synthase MTR A2756G (rs1805087) polymorphism is inconclusive based on data from past studies. Hence, this updated meta-analysis was conducted to investigate the relationship between methionine synthase reductase (MTR) rs1805087 polymorphism and hematological cancers. Method: We searched EMBASE, Google Scholar, Ovid and PubMed databases for possible relevant articles up to December 31, 2019. Results: The overall pooled outcome of our analysis showed lack of association between the risk of hematological malignancies and MTR A2756G polymorphism under the allele model (G vs A: odds ratio = 1.001, 95% CI: 0.944–1.061; p = 0.983), recessive model (GG vs GA + AA: odds ratio = 1.050, 95% CI: 0.942–1.170; p = 0.382). Conclusion: The findings in this study demonstrate a lack of relationship between hematological cancers and MTR A2756G.


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