INTERRELATION OF ALLELIC VARIANTS OF HEMOSTASIS SYSTEM GENES ON THE DEVELOPMENT AND COURSE OF LUPUS NEPHRITIS

2019 ◽  
Vol 23 (2) ◽  
pp. 77-81
Author(s):  
E. N. Borisov ◽  
L. V. Ivanitsky ◽  
L. M. Samokhodskaya ◽  
T. N. Krasnova ◽  
E. P. Pavlikova ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Mutant Allele ◽  
Impaired Renal Function ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Renal Survival ◽  
Mutant Genotype ◽  
Hemostatic System ◽  
Allelic Variations ◽  
Pai 1

THE AIM: to evaluate the effect of allelic variations in the hemostatic system genes on the development and course of lupus nephritis. PATIENTS AND METHODS. The study analyzed 100 patients with SLE Caucasians. 80 women and 20 men aged 16 to 73 years (mean age 37, ± 14 years). The duration of observation was for 73 patients over 5 years, for 18 – from 1 year to 5 years and for 9 – less than 1 year A rise in the level of creatinine in the blood above or equal to 2 mg / dl was considered a significant sign of impaired renal function. RESULTS. Among the patients included in the study, kidney damage was detected in 61 people (61%). In 33 of them (54.1%), a variant of renal pathology was observed according to the type of rapidly progressive lupus nephritis (BPVN). In patients with BH, mutations in the MTHFR (C677T) gene were statistically significantly more frequent (p = 0.033). The OR for the mutant genotype is 6.146 with 95% CI from 1.692 to 22.326. In patients with PWHD, mutations in the MTHFR (C677T) gene were statistically significantly more frequent (p = 0.031). The OR for the mutant genotype is 1.625 with 95% CI from 1.034 to 4.771. The five-year renal survival in carriers of the mutant allele of the MTHFR gene (C677T) is statistically significantly lower (72.8%) than in patients without this mutation (81.9%) (p = 0.027). Ten-year renal survival in carriers of the mutant allele of the MTHFR gene (C677T) is statistically significantly less (55.6%) than in patients without this mutation (70.5%) (p = 0.016). In patients with BH, mutations in the PAI-1 gene (4G / 5G 675) were statistically significantly more frequent (p = 0.046). OR for mutant genotype – 1.766 with 95% CI from 1.061 to 4.758. CONCLUSION. The mutant alleles of the MTHFR (C677T) and PAI-1 (4G / 5G 675) genes are likely to be associated with the development of BH. Polymorphism of the MTHFR gene (C677T) is associated with an unfavorable course of HH.

scholarly journals Polymorphisms variants of the MTHFR C677T and PAI-1 5G/4G genes and their combinations in the group of children with arterial ischemic stroke

2020 ◽  
Vol 29 (58) ◽  
pp. 27-32
Author(s):  
Nataliya Smulska ◽  
◽  
Zoia Rossokha ◽  
Liliya Fishchuk ◽  
Nataliya Gorovenko ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Direct Interaction ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
Study Group ◽  
Arterial Ischemic Stroke ◽  
Group Detection ◽  
Polymorphic Variants ◽  
Pai 1

Introduction. Arterial ischemic stroke (AIS) in childhood is a disorder associated with different predisposing factors, thrombophilia is one of them. We present the study of the MTHFR C677T and PAI-1 5G/4G gene polymorphisms as a possible risk factor for the development of AIS in the group of Ukrainian children. Materials and methods. 77 children from 29 days to 15 years of age were involved in this study: study group - 44 children with AIS, and 33 in a control group. Children enrolled to both groups were at similar age. Results. In the study group there was an increase in the frequency of genotypes 677CT (OR = 2.69) and 677TT, CT + TT genotypes (OR = 3.67) of the MTHFR gene, increased frequency of the 677T allele (OR = 2.57). In the study group detection of 5G/5G + 5G/4G genotypes was higher (OR = 2.82) with statistically predominance of the 5G allele (OR = 2.26) of the gene PAI -1. Higher frequency of the combination of genotypes genes 677CT + 5G/5G was found in the main group. The model of interpreting interactions was built, it allows to predict indirectly the potential intergenic interactions. Conclusions. We conclude that risk of AIS is higher in children with polymorphic variants 677CT and 677TT for the MTHFR gene; the association of polymorphic variants 5G/4G and 5G/5G for the PAI-1 gene with a decrease in the risk of developing AIS; direct interaction with the MTHFR was found for PAI-1, but of weak strength

The extent of tubulointerstitial inflammation is an independent predictor of renal survival in lupus nephritis

2021 ◽  
Author(s):  
Manuel Ferreira Gomes ◽  
Claudia Mardones ◽  
Marc Xipell ◽  
Miquel Blasco ◽  
Manel Solé ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Independent Predictor ◽  
Renal Survival ◽  
Tubulointerstitial Inflammation

Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review

2021 ◽  
pp. 112067212110006
Author(s):  
Manuel Marques ◽  
Francisco Alves ◽  
Miguel Leitão ◽  
Catarina Rodrigues ◽  
Joana Tavares Ferreira
Keyword(s):  
Risk Factors ◽  
Literature Review ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Mthfr Polymorphisms ◽  
Vein Occlusion ◽  
C677t Mutation ◽  
Retinal Vascular Disease

The role of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene in retinal vein occlusion (RVO) is a theme of discussion since the first reports of RVO in patients with MTHFR C677T mutation and without classic acquired risk factors for retinal vascular disease. The association between MTHFR polymorphisms and RVO has been studied over the last 20 years producing conflicting results. This review aims to summarize the literature concerning the role MTHFR polymorphisms as risk factors for RVO.

scholarly journals FRI0181 ORGAN DAMAGE FREE SURVIVAL IN SOUTHERN CHINESE PATIENTS WITH ACTIVE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 674.1-674
Author(s):  
C. C. Mok ◽  
C. S. Sin ◽  
K. C. Hau ◽  
T. H. Kwan
Keyword(s):  
Lupus Nephritis ◽  
Regression Model ◽  
Cox Regression ◽  
Organ Damage ◽  
Renal Survival ◽  
Cox Regression Model ◽  
Free Survival ◽  
Renal Response

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared

scholarly journals Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment

CNS Spectrums ◽  
2012 ◽  
Vol 17 (2) ◽  
pp. 76-86 ◽  
Author(s):  
David Mischoulon ◽  
Stefania Lamon-Fava ◽  
Jacob Selhub ◽  
Judith Katz ◽  
George I. Papakostas ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mthfr C677t ◽  
Response Rates ◽  
Mthfr Gene ◽  
Methionine Synthase ◽  
Antidepressant Response ◽  
Major Depressive ◽  
Fluoxetine Treatment ◽  
Intent To Treat

AbstractObjectiveTo examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response.MethodsWe screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20–60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined.ResultsPrevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C = 41%, C/T = 47%, T/T = 11%, A/A = 66%, A/G = 29%, G/G = 4%). In the fluoxetine-treated subsample (n = 49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response.ConclusionThe C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples.

scholarly journals Study of genes involved in angiogenesis and metabolic processes of peripheral blood lymphocytes in patients with chronic endometritis

2021 ◽  
Vol 38 (4) ◽  
pp. 25-35
Author(s):  
E. G. Kobaidze
Keyword(s):  
Clinical Manifestations ◽  
Mthfr C677t ◽  
Peripheral Blood Lymphocytes ◽  
Mthfr Gene ◽  
Reproductive Period ◽  
Enos Gene ◽  
Metabolic Processes ◽  
Chronic Endometritis ◽  
Blood Lymphocytes ◽  
Healthy Women

Objective. To study the polymorphisms of the genes involved in angiogenesis and in metabolic processes, to assess the level of lymphocytes in patients with chronic endometritis and practically healthy women of reproductive period. Materials and methods. 86 patients were examined; DNA regions of the genes eNOS 1799983 (Glu298Asp), PPARA (G2528C), ApoE rs429358 (Cys130Arg), MTHFR (C677T, A1298C) were used as primers; blood lymphocytes (CD3+, CD4+, CD8+, CD19+, CD95+) were assessed. Results. Statistically significant differences in gynecological and chronic somatic pathology were obtained in patients with chronic endometritis; they more often than practically healthy women had polymorphisms of the genes ApoE rs429358, eNOS1799983, PPARA (G2528C); patients with chronic endometritis more often had dysregulation of the immune system in the form of insufficiency of the cellular effector link of immunity and changes in the PPARA, ApoE, eNOS gene. Attention was drawn to the obtained relationships of polymorphic genes and clinical manifestations in patients with chronic endometritis, in particular, with a history of non-developing pregnancy in anamnesis, there was more often detected polymorphism of the ApoE gene, with abnormal uterine bleeding polymorphism of PPARA, with chronic inflammatory pathology of the gallbladder polymorphism of the MTHFR gene. Conclusions. The prevalence of polymorphism of the genes eNOS 1799983 (Glu298Asp), PPARA (G2528C), ApoE rs429358 (Cys130Arg), MTHFR (C677T, A1298C) was obtained in patients with chronic endometrial inflammation compared with practically healthy participants in the study. Insufficiency of the cellular effector link of immunity was revealed in the majority of patients with ChE and an association with allele C genotypes G/C and C/C of PPARA 4253778 gene, with allele C genotypes G/C and C/C of ApoE42935 gene, with allele C genotypes G/C and C/C of eNOS 1799983 gene and G/C genotype of MTHFR gene (C677T, A1298C).

Association between FVL G1691A, MTHFR C677T and A1298C Polymorphisms with Risk for Retinopathy of PrematurityAssociation between FVL G1691A, MTHFR C677T and A1298C Polymorphisms with Risk for Retinopathy of Prematurity

2021 ◽  
Author(s):  
Hamideh Shajari ◽  
Mohammadamin Ghadyani ◽  
Seyed Hamed Hosseini-Jangjou ◽  
Reza Bahrami ◽  
Seyed Alireza Dastgheib ◽  
...  
Keyword(s):  
Retinopathy Of Prematurity ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Factor V ◽  
Background Retinopathy ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Rflp Assay ◽  
Preventable Blindness

Background: Retinopathy of prematurity (ROP) is an important cause of preventable blindness in children. The aim of this study was to examine the association of the polymorphisms at Factor V Leiden (FVL) and methylene tetrahydrofolate reductase (MTHFR) gene with risk of ROP. Methods: A total of 106 neonates with ROP and 110 healthy neonates were enrolled. The FVL G1691A and MTHFR C677T and A1298C polymorphisms were genotyped by PCR-RFLP assay. Results: There was a significant association between FVL G1691A polymorphism and an increased risk of ROP. However, the MTHFR C677T and A1298C polymorphisms were not associated with risk of ROP. Conclusion: FVL G1691A polymorphism may be risk factor for development of ROP in neonates. However, there was no significant association between MTHFR C677T and A1298C polymorphisms and risk of ROP. However, it is critical that larger and well-designed studies in different ethnicities are needed to confirm our conclusions.

The Crescentic Implication of Renal Outcomes in Proliferative Lupus Nephritis

2018 ◽  
Vol 45 (4) ◽  
pp. 513-520 ◽  
Author(s):  
Fanghao Cai ◽  
Fei Han ◽  
Hongya Wang ◽  
Haidongqin Han ◽  
Jingyun Le ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lupus Nephritis ◽  
Renal Survival ◽  
Endstage Renal Disease ◽  
Tubular Atrophy ◽  
Renal Outcomes ◽  
Proliferative Lupus Nephritis ◽  
Independent Risk Factors ◽  
Cox Proportional Hazard Regression ◽  
Renal Tubular

Objective.To determine the association between crescents and renal outcomes, and the implications on therapeutic choices.Methods.There were 231 patients with biopsy-proven proliferative lupus nephritis (PLN) who were divided into 4 groups: 59 patients were in the noncrescent group (NC); 59 patients exclusively with segmental crescents were in the segmental crescent group (SC); patients with circumferential crescents were categorized into 2 groups according to the crescentic ratio (C1 had 64 patients with ≤ 25%, and C2 had 49 patients with > 25%). Their baseline laboratory tests, histopathological manifestations, and outcomes were compared.Results.Remission rates in NC, SC, C1, and C2 groups were 92.1%, 85.4%, 95.0%, and 76.1%, respectively. Fewer patients in the C2 group achieved complete remission than the other 3 groups. For longterm outcomes evaluated by serum creatinine (SCr) doubling or endstage renal disease (ESRD), the renal survival rate was lowest in the C2 group (p = 0.003). Including clinical and pathological variables in the Cox proportional hazard regression model separately, the multivariate analysis revealed that these were independent risk factors for SCr doubling or ESRD: baseline SCr (with every 1 mg/dl increase: HR = 1.834, 95% CI 1.465–2.296; p < 0.001), hemoglobin (with every 1 g/l increase: HR = 0.970, 95% CI 0.947–0.992; p = 0.009), the proportions of cellular crescents (with every 1% increase: HR = 1.040, 95% CI 1.015–1.066; p = 0.002) and fibrocellular crescents (with every 1% increase: HR = 1.085, 95% CI 1.013–1.163; p = 0.020), and severe renal tubular atrophy (HR = 5.348, 95% CI 1.278–22.373; p = 0.022).Conclusion.PLN with crescents > 25% had worse renal outcomes both in short and long terms. Proportions of cellular and fibrocellular crescents were independent risk factors for poor renal survival.

scholarly journals Renal Remission Status and Longterm Renal Survival in Patients with Lupus Nephritis: A Retrospective Cohort Analysis

2018 ◽  
Vol 45 (5) ◽  
pp. 671-677 ◽  
Author(s):  
Julie E. Davidson ◽  
Qinggong Fu ◽  
Beulah Ji ◽  
Sapna Rao ◽  
David Roth ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Cox Regression ◽  
Cohort Analysis ◽  
Standard Of Care ◽  
Renal Survival ◽  
Endstage Renal Disease ◽  
American College Of Rheumatology ◽  
Remission Status ◽  
Kaplan Meier ◽  
Remission Criteria

Objective.This observational study was a retrospective analysis of prospectively collected Hopkins Lupus Cohort data to compare longterm renal survival in patients with lupus nephritis (LN) who achieved complete (CR), partial (PR), or no remission following standard-of-care LN induction therapy.Methods.Eligible patients with biopsy-proven LN (revised American College of Rheumatology or Systemic Lupus Collaborating Clinics criteria) were identified and categorized into ordinal (CR, PR, or no remission) or binary (response or no response) renal remission categories at 24 months post-diagnosis [modified Aspreva Lupus Management Study (mALMS) and modified Belimumab International Lupus Nephritis Study (mBLISS-LN) criteria]. The primary endpoint was longterm renal survival [without endstage renal disease (ESRD) or death].Results.In total, 176 patients met the inclusion criteria. At Month 24 postbiopsy, more patients met mALMS remission criteria (CR = 59.1%, PR = 30.1%) than mBLISS-LN criteria (CR = 40.9%, PR = 16.5%). During subsequent followup, 18 patients developed ESRD or died. Kaplan–Meier plots suggested patients with no remission at Month 24 were more likely than those with PR or CR to develop the outcome using either mALMS (p = 0.0038) and mBLISS-LN (p = 0.0097) criteria for remission. Based on Cox regression models adjusted for key confounders, those in CR according to the mBLISS-LN (HR 0.254, 95% CI 0.082–0.787; p = 0.0176) and mALMS criteria (HR 0.228, 95% CI 0.063–0.828; p = 0.0246) were significantly less likely to experience ESRD/mortality than those not in remission.Conclusion.Renal remission status at 24 months following LN diagnosis is a significant predictor of longterm renal survival, and a clinically relevant endpoint.

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