The value of the MTHFR polymorphisms in pathogenesis of nontraumatic necrosis of femoral head

2020 ◽  
Vol 27 (2) ◽  
pp. 19-23
Author(s):  
Mikhail A. Panin ◽  
Nikolai V. Zagorodnii ◽  
Larisa M. Samokhodskaya ◽  
Andrei V. Boiko
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Lupus Erythematosus ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Main Group ◽  
Cytotoxic Agents ◽  
Control Group ◽  
Mthfr Polymorphisms ◽  
C677t Mthfr

Introduction. Among the etiological factors of non-traumatic avascular necrosis of the femoral head are the following: the prolonged use of corticosteroids, alcohol abuse, systemic lupus erythematosus, sickle cell anemia, the Legg Calve Perthes disease, ionizing radiation, cytotoxic agents, etc. At the same time necrosis of the femoral head might occur in the absence of the above factors (idiopathic necrosis). The reasons for idiopathic avascular necrosis could be a mechanical obstacle to the flow of blood, thrombotic occlusion of vessels, extravascular compression. The purpose of this study is to examine the role of C677T gene mutation of the MTHFR gene in the development of non-traumatic avascular necrosis of the femoral head. Materials and methods. During this study there was a comparative analysis of the frequency of the C677T gene allelic variants conducted in 41 patients with a verified diagnosis of non-traumatic avascular necrosis (main group) and 320 healthy individuals (control group). The survey program included the study of polymorphisms of MTHFR C677T gene by PCR. Results. Differences in the frequency of occurrence of C allele of C677T gene MTHFR in the heterozygous state in case of non-traumatic avascular necrosis and in its absence were not statistically significant (51.2% against 37.2% respectively, 2 = 3.014, p = 0.083). The genotype TT (T in the homozygous state) of the C677T MTHFR gene was detected in 19.5% of the main group patients. A similar index in the control group was two times lower and amounted to 9.0 percent, the differences between groups statistically significant, 2 = 4.314, p = 0.038. Conclusion. The study showed the importance of having the T C677T MTHFR gene in the pathogenesis of non-traumatic avascular necrosis of the femoral head. The data obtained and the analysis of the current literature suggests that this polymorphism is one of genetic predictors of non-traumatic avascular necrosis of the femoral head and other cardiovascular diseases as well.

scholarly journals Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism

2020 ◽  
Vol 07 (02) ◽  
pp. 047-050
Author(s):  
Tamar Kvaratskhelia ◽  
Elene Abzianidze ◽  
Ketevan Asatiani ◽  
Merab Kvintradze ◽  
Sandro Surmava ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Fragment Length Polymorphism ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
Healthy Individuals ◽  
Chain Reaction ◽  
Mthfr Polymorphisms ◽  
Polymerase Chain ◽  
Hypothyroid Patients

AbstractThe aim of this study was to investigate the frequency of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in Georgian females with hypothyroidism. Thirty-four patients and 29 healthy individuals were recruited in this study. Polymerase chain reaction-restriction fragment length polymorphism analyses were used for genotyping of MTHFR polymorphisms. The results of this study suggest that the MTHFR C677T variant was significantly associated with hypothyroidism. In addition, in individuals with T allele risk of hypothyroidism significantly increased. Combination of CT/AA genotypes was more prevalent in the hypothyroid patients than in the control group. Thus, C677T polymorphism could be a possible genetic factor contributing to the pathophysiology of hypothyroidism, possibly through hyperhomocysteinemia.

Genetic Polymorphisms of Methylenetetrahydrofolate Reductase Genes and Diffuse Large B-Cell Lymphoma Risk in Middle Eastern Population.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4609-4609
Author(s):  
Abdul K. Siraj ◽  
Rong Bu ◽  
Mona Ibrahim ◽  
Maha Al-Rasheed ◽  
Shahab Uddin ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Case Control Study ◽  
B Cell Lymphoma ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
Mthfr Polymorphisms ◽  
Activity Group ◽  
Large B Cell Lymphoma ◽  
Control Study

Abstract Diffuse large B-Cell Lymphoma (DLBCL) is one of the most common non-Hodgkin lymphoma types and increased incidence has also been reported during the past 30 years. Methylenetetrahydrofolate (MTHFR) balances the pool of folate coenzymes in one carbon metabolism of DNA synthesis and methylation, both are implicated in carcinogenesis of many types of cancer including lymphoma. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate caner predisposing factor. These genetic differences are highly race specific and have never been screened in the Saudi DLBCL patients. We conducted hospital-based case control study in the Saudi DLBCL patients. To evaluate the MTHFR C677T and A1298C functional polymorphisms in the MTHFR gene and their association with Saudi DLBCL risk. A hospital based case control study was conducted on a Saudi population- which is known for their genetic homogeneity and high consanguinity- consisting of 187 histologically confirmed DLBCL cases and 513 Saudi controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping. Data showed that Saudi individuals carrying MTHFR 1298 CC genotype (p<0.001) and genotypes carrying MTHFR 1298C allele (p= 0.012) had 4.23 and 1.73-fold higher risk of developing DLBCL, respectively. Additionally, combined genotype CCCC (MTHFR 677CC+ MTHFR 1298CC) among intermediate MTHFR activity group was associated with 3.489 fold and CTCC (MTHFR 677 CT + 1298CC) among low MTHFR activity group was related to 9.515 fold higher risk, compared with full MTHFR enzyme activity. Our findings suggest that polymorphisms of MTHFR enzyme genes support for the important role of folate metabolism in lymphomagenesis and may be associated with the individual susceptibility to develop DLBCL in Saudi Arabian population. Table 1 Distribution of MTHFR polymorphisms in healthy population and lymphoma patients. Polymorphism Genotype Control group Lymphoma patients p -Methylenetetrahydrofolate reductase (MTHFR) MTHFR C677T CC 372 (72.8%) 109 (68.1%) CT 126 (24.7%) 45 (28.1%) 0.346 1.219 TT 13 (2.5%) 6 (3.8%) 0.404 1.575 CT+TT 139 (27.2%) 51 (31.9%) 0.269 1.252 MTHFR A1298C AA 239 (46.8%) 38 (33.6%) AC 220 (43.1%) 40 (35.4%) 0.625 1.144 CC 52 (10.2%) 35 (31%) <0.001 4.233 AC+CC 272 (53.2%) 75 (66.4%) 0.012 1.734 Table 2 Distribution of combined C677T and A1298C MTHFR genotypes in case and control group. Genotype Control Case p OR ND=Not detected Full Activity group CCAA 157 (30.8%) 22 (27.8%) Intermediate Activity group CCAC 169 (33.2%) 28 (35.4%) 0.649 1.182 CCCC 45 (8.8%) 22 (27.8%) <0.001 3.489 CTAA 69 (13.6%) 13 (16.5%) 0.439 1.345 TOTAL 283 63 0.104 1.589 Low Activity Group CTAC 50 (9.8%) 5 (6.3%) 0.634 0.714 CTCC 6 (1.2%) 8 (10.1%) <0.001 9.515 TTAA 12 (2.4%) 1 (1.3%) 1 0.595 TTAC 0 2 (2.5%) 0.017 ND TTCC 1 (0.2%) - - - TOTAL 69 16 0.189 1.655 Intermediate + Low 352 (69.1%) 79 0.073 1.602

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 The significance of polymorphisms of gene coagulation factors VII and XIII in the pathogenesis of non-traumatic avascular necrosis of the femoral head

2021 ◽  
Vol 27 (1) ◽  
pp. 43-47
Author(s):  
M.A. Panin ◽  
◽  
N.V Zagorodnii ◽  
A.V. Boiko ◽  
L.M. Samokhodskaya ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Coagulation Factors ◽  
Group Differences ◽  
Unknown Etiology ◽  
Control Group ◽  
Study Group ◽  
Control Groups ◽  
Aseptic Necrosis ◽  
And Control

Introduction Non-traumatic avascular necrosis of the femoral head (ANFH) is a poly-etiologic and socially significant disease in the age of 20 to 50 years and is associated with disability. Research on the identification of necrosis causes/predictors is a relevant issue. Purpose To study the contribution of polymorphisms in the genes of coagulation factors F7 and F13 in the aetiology of non-traumatic avascular necrosis of the femoral head. Methods Polymorphisms of the genes of coagulation factors F7 and F13 were studied; comparative analysis of the frequency of important allelic variants of F7genes (Arg353Gln) and F13 (Val134Leu) in patients with a verified diagnosis of aseptic necrosis (study group) and in healthy patients (control group) was performed. The study group included 41 patients (all males) with aseptic necrosis of the femoral head of unknown etiology. Results The frequency of gene alleles in the F7 Arg353Gln in the study group were: GG in 30 out of 41 patients (73.2 %), GA in 11 out of 41 patients (26.8 %), and none of 41 patients had a polymorphic variant AA. The frequency of alleles of this type of gene in the control group was as follows: GG in 7 out of 320 subjects (2.2 %), GA in 66 out of 320 patients (20.6 %), AA in 247 out of 320 (77.2 %). Significant differences were identified in the frequencies of homozygous genotypes, AA (χ2 = 100.215, p < 0.001) and GG (χ2 = 205.770, p < 0.001) in the study and control groups respectively. As for the heterozygous GA genotype, the differences were not significant (χ2 = 0.834, p = 0.362). The GG genotype of the gene Val134Leu F13 WAS 2.8 times more frequent in patients of the study group, differences were statistically significant (26.8 % against 9.7 %, χ2 = 10.388; p = 0.002). The presence of the TT genotype of the gene Val134Leu F13 was almost five times more frequent (χ2 = 18.956, p < 0.001) in healthy individuals (control group). Differences in the frequency of allele T in homo/ and heterozygous combinations (TT and GT) in the study and control groups was also significant (72.7 % vs 90.1 %, respectively, χ2 = 4.946, p = 0.027). Discussion Polymorphisms of coagulation factors genes F7 and F13 have a significant effect on the genesis of non-traumatic avascular necrosis of the femoral head. Risk factor of ANFH development is homozygous GG genotype in the gene Arg353Gln F7. Low probability of the disease is due to a protective role of AA genotype of the gene Arg353Gln F7 and TT genotype of the gene Val134Leu F13.

scholarly journals Evaluation of c677t and a1298c polymorphism of the methylenetetrahydrofolate reductase gene as a maternal risk factor for trisomy 21 (a monocentric study)

2017 ◽  
Vol 25 (1) ◽  
pp. 27-35
Author(s):  
Simona Bucerzan ◽  
Radu Anghel Popp ◽  
Raluca Maria Vlad ◽  
Cecilia Lazea ◽  
Radu Nicolaescu ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Control Group ◽  
Healthy Children ◽  
Mthfr Polymorphisms ◽  
Maternal Risk ◽  
Reductase Gene ◽  
A1298c Polymorphism ◽  
Methylenetetrahydrofolate Reductase Gene

Abstract Aim: To assess the risk for trisomy 21 in children, depending on the polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in mothers. Methods: For 93 mothers who have children with trisomy 21 and 202 mothers of healthy children (control group), genotyping of MTHFR polymorphisms C677T and A1298C was performed. Results: For each polymorphism, three genotypes were identified (normal homozygous, heterozygous and mutant homozygous). For the polymorphism C677T, the frequencies of the three genotypes (CC, CT and TT) were 50.5%, 40.8% and 8.6% in mothers of children with trisomy 21, versus 42.6%, 46% and 11.4% in mothers of healthy children, with no statistically significant differences. The frequency of the polymorphism A1298C was not statistically significant between the two groups for the genotype (AA) (48.4% vs 56.4%) or the genotype (AC) (39.8% vs 38.6%), but the genotype TT was more frequent in mothers of children with trisomy 21 (11.8% vs 4.9%; p = 0.033; OR = 2.57). Conclusion: Women with genotype CC for the polymorphism A1298C of the MTHFR gene have a 2.57 times higher risk of offspring with trisomy 21.

scholarly journals Genetic Bases of VitaminB12 Deficiency: Impact of MTHFR, TCN-II and GIF Polymorphisms on Vitamin B12 Level

2022 ◽  
Vol 19 ◽  
pp. 10-13
Author(s):  
Mazhar Salim Al Zoubi
Keyword(s):  
Vitamin B12 ◽  
Neurological Disorders ◽  
Molecular Basis ◽  
Vitamin B12 Deficiency ◽  
Mthfr Gene ◽  
Control Group ◽  
Mthfr Polymorphisms ◽  
Jordanian Population ◽  
B12 Deficiency ◽  
The Impact

Vitamin B12 deficiency is associated with serious health problems such as neurological disorders. In Jordan, few studies have evaluated the level of vitamin B21 in the Jordanian population with different prevalence. Genetic predisposition, lifestyle, environment, socioeconomic status, and geographic have been linked to vitamin B12 deficiency. Polymorphisms in the GIF, MTHFR, and Transcobalamins, have been proposed to be associated with the level of vitamin B12. The aim of the current study was to evaluate the impact of certain polymorphisms in MTHFR, TCN-II and GIF genes on the level of vitamin B12 in the Jordanian population. Polymorphic sites of the MTHFR (c.677 C>T, rs1801133 and c.1286A>C, rs1801131), TCN2-776C>G (Arg259Pro) (rs1801198) and GIF-68 A>G (Q5R) genes were analyzed by RFLP and DNA sequencing in a group of vitamin B12 deficient individuals (n = 100). The control group included 100 matching individuals with a normal level of vitamin B12 (>200 ng/mL). Our results showed a significant association between the homologous variant of the TCN2 gene (G776G) and MTHFR c.677C>T genes and vitamin B12 deficiency. On the other hand, The MTHFR c.1286A>C variant and GIF variants did not show significant association with vitamin B12 deficiency. This study expounds the association of TCN2 and MTHFR polymorphisms with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2, GIF, and MTHFR gene polymorphisms on vitamin B12 deficiency and associated disorders.

A case-control study investigating the effect of MTHFR C677T variant on performance of elite athletes

2020 ◽  
Vol 20 ◽  
Author(s):  
Ayse Feyda Nursal ◽  
Serbulent Yigit ◽  
Husniye Rustemoglu ◽  
Abdullah Cenikli
Keyword(s):  
Athletic Performance ◽  
Methylenetetrahydrofolate Reductase ◽  
Elite Athletes ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
Genotype Distribution ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Strength Of Association

Objective: Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects the elite athletic performance. Methods: This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes had (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. Conclusion: Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

scholarly journals Plasma Homocysteine Level And C677T Polymorphism In MTHFR Gene In Patients With Acute Coronary Syndrome

2015 ◽  
Vol 8 (1) ◽  
pp. 46-51
Author(s):  
Andrey V. Grek ◽  
Lyudmyla N. Prystupa ◽  
Tatiana V. Sytnik
Keyword(s):  
Acute Coronary Syndrome ◽  
Endothelial Dysfunction ◽  
Homocysteine Level ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
C677t Polymorphism ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Coronary Syndrome

SummaryCardiovascular diseases (CVD) of atherosclerotic origin and accompanying complications are a major cause of mortality in the world and Ukraine, in particular. Endothelial dysfunction is the key cause of atherosclerosis and atherothrombosis. One of the causes of endothelial dysfunction is hyperhomocysteinemia that may occur on the background of MTHFR (methylenetetrahydrofolate reductase) mutation.Thus, the goal of the study was to investigate the interrelation between homocysteine (Hc) level and MTHFR polymorphism in patients with acute coronary syndrome (ACS).161 patients with ischemic heart disease and ACS have been examined. The control group comprised 87 healthy individuals. Homocysteine level was the highest in the patients having ACS with ST-segment elevation and complicated course, and was 1.8 times higher than Hc level in the control group. The patients with the most severe ACS course comprised 27 % of homozygotes for the major allele C and 41 % of homozygotes for the minor allele T. Comparing the distribution of MTHFR gene C677T polymorphism in patients with ACS that were stratified by plasma Hc level, we observed a statistically significant association, P < 0.030 by chi-square test. We confirmed that these patients had a high T/T genotype frequency of MTHFR C677T polymorphism. The obtained data proved the association of T/T genotype of MTHFR C677T polymorphism with increased Hc level as well as ACS severity.

scholarly journals Association Study of MTHFR Polymorphisms with Nonarteritic Anterior Ischemic Optic Neuropathy in a Spanish Population

2020 ◽  
Vol 5 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Beatriz Fernández-Vega ◽  
Lydia Álvarez ◽  
Montserrat García ◽  
Enol Artime ◽  
Marta Diñeiro Soto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Optic Neuropathy ◽  
Mthfr Gene ◽  
Spanish Population ◽  
Anterior Ischemic Optic Neuropathy ◽  
Control Group ◽  
Ischemic Optic Neuropathy ◽  
Mthfr Polymorphisms ◽  
Risk Variants ◽  
Local Risk

Introduction: Nonarteritic anterior ischemic optic neuropathy (NAION), painless loss of central and/or peripheral vision, is a multifactorial disease caused by insufficient blood flow through the posterior ciliary arteries to the optic nerve head. Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene, triggering hyperhomocysteinemia as a consequence of a decreased activity of the codified enzyme, have been considered to be among the risk factors of NAION. Objective: The main aim was to study the association of the most common MTHFR genetic polymorphisms C677T and A1298C with NAION in a Spanish population. Methods: In this case-control study, the association of the most common MTHFR polymorphisms was investigated in 94 unrelated native Spanish patients diagnosed with NAION and 204 healthy controls. Two single nucleotide polymorphisms located in the MTHFR gene, C677T (rs1801133) and A1298C (rs1801131), were analyzed by DNA sequencing and TaqMan assays. Results: The allelic and genotypic frequencies of the MTHFR variants obtained in the NAION group were not significantly different when compared with the control group. A higher frequency of the C677T/A1298C genotype, codifying the nonmutated MTHFR form, was obtained in control subjects (11.27%) compared to NAION patients (4.26%), suggesting a protective effect of the wild-type protein, although this result was not conclusive considering the obtained confidence interval (CI) (95% CI: 0.13–1.06). Study of additional clinical factors including hypertension, diabetes mellitus, and dyslipidemia showed no association with a higher risk of NAION. Conversely, the clinical history of heart or cerebrovascular diseases was significantly higher in NAION patients compared to controls. Over the world, risk variants of the MTHFR gene are highly frequent, excluding African black populations, indicating a racial influence. Conclusions: The MTHFR variants did not significantly increase the risk of suffering from NAION. However, considering that individuals with at least one of the risk variants have the MTHFR enzyme with decreased activity, it cannot be ruled out that these mutations are relevant for the development of NAION in a subgroup of the population with other specific characteristics. These may include high plasma levels of homocysteine along with nutritional deficiencies including low folate or vitamin B12 and the combination of systemic and local risk factors.

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