MTHFR Polymorphisms Research Articles

Association analysis of MTHFR (rs1801133 and rs1801131) and MTRR (rs1801394) gene polymorphisms towards the development of hypertension in the Bai population from Yunnan, China

ABSTRACT Objective Hypertension is one of the leading causes of human death and disability. MTHFR and MTRR regulate folate metabolism and are closely linked to hypertension, although the relationship is inconsistent among different ethnic groups. The present study aims to investigate the effects of MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), and MTRR A66G (rs1801394) polymorphisms on hypertension susceptibility in the Bai nationality of the Yunnan Province, China. Methods This case–control study included 373 hypertensive patients and 240 healthy controls from the Chinese Bai population. The genotyping of MTHFR and MTRR gene polymorphisms was carried out by using the KASP method. The effects of genetic variations of MTHFR and MTRR genes on hypertension risk were evaluated with odds ratios (OR) and 95% confidence intervals (95% CI). Results The present study revealed that the CT and TT genotypes and T allele of MTHFR C677T locus were considerably associated with an increased risk of hypertension. In addition, MTHFR A1298C locus CC genotype could significantly increase the hypertension risk. The T-A and C–C haplotypes of MTHFR C677T and MTHFR A1298C could increase the risk of hypertension. Further stratified analysis by risk rank of folate metabolism indicated that people with poor utilization of folic acid were more prone to develop hypertension. In the hypertension group, the MTHFR C677T polymorphism was significantly associated with fasting blood glucose, fructosamine, apolipoprotein A1, homocysteine, superoxide dismutase, and malondialdehyde levels. Conclusion Our study suggested that genetic variations of MTHFR C677T and MTHFR A1298C were significantly associated with susceptibility to hypertension in the Bai population from Yunnan, China.

Associations of MTHFR Polymorphisms and Cytosine Modifications with Early-Gestational Diabetes Mellitus in Chinese Pregnant Women.

Early-Gestational Diabetes Mellitus (Early-GDM) is a complex condition that may cause complications in infants of affected mothers. The aim of this case-control study was to analyze the effects of genetic-epigenetic interaction on Early-GDM and fetal development with respect to cytosine modifications (i.e., 5mC, 5-methylcytosines; and 5hmC, 5-hydroxymethylcytosines) and single nucleotide polymorphisms (SNPs) of MTHFR, a key gene involving cytosine modifications. Peripheral blood samples were collected from 92 women in their first or second trimester of pregnancy (Early-GDM, n = 14; Controls, n = 78). Global DNA 5mC and 5hmC were quantified by HPLC-MS/MS, and MTHFR SNPs (rs1801133 C > T and rs1801131 A > C) were determined by TaqMan-qPCR. Association analysis suggested that MTHFR rs1801133 TT genotype was a risk factor of Early-GDM (OR [odds ratio] = 4.00; 95% CI [confidence interval]: 1.24, 12.86; p = 0.02). The C allele of rs1801131 appeared to be a protective factor for the 2-h OGTT (oral glucose tolerance test) (OR = -0.79; 95% CI: -1.48, -0.10; p = 0.03). Patients with Early-GDM had higher global 5mC and lower global 5hmC. The reduction of global 5hmC and the TT genotype of rs1801133 were associated with higher level of the 1st-FBG (fasting blood glucose in the first trimester) (p < 0.05). Additionally, global 5mC showed a positive correlation with birth weight, body length and head circumference of newborns, while global 5hmC showed a negative correlation with birth weight. The current study implicated MTHFR SNPs and cytosine modifications in the development of Early-GDM and potential complications in their newborns.

Prevalence of MTHFR polymorphisms and metabolic outcomes in Chilean women with Polycystic Ovary Syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The impact of single nucleotide polymorphisms in MTHFR and MTRR genes on disease activity and the presence of methotrexate treatment side effects in children with juvenile idiopathic arthritis.

To determine the impact of single nucleotide polymorphisms (SNPs) in MTHFR and MTRR genes on disease activity and the presence of MTX therapy adverse events in Polish children with juvenile idiopathic arthritis (JIA). SNP genotyping was performed using genomic DNA isolated from peripheral blood samples. Patients with MTHFR rs1801133 CT/TT variant had higher values of inflammatory markers, number of joints with active arthritis, and JADAS-71 value at the baseline of MTX treatment. Children with MTRR rs1801394 AG/AA variant presented higher inflammatory marker values at JIA diagnosis. MTHFR rs1801133 and MTRR rs1801394 polymorphisms are associated with higher disease activity at the moment of JIA diagnosis.

Kötü obstetrik öyküsü ve deri hastalıkları olan kadınlarda anti-parietal hücre antikor pozitifliği: gebelik öncesi danışmanlığın önemi

Purpose: The aim of this study was vto demonstrate the impact of anti-parietal cell antibody (APCA) positivity in women with poor obstetric history and skin disorders.&#x0D; Materials and Methods: This retrospective cohort consisted of 63 women having skin disorders and poor obstetric history. Patients were grouped into the control (women with skin disorders only, n=50) and study groups (women with skin disorders and APCA positivity, n=13). The study groups were compared in terms of demographic findings, BOI, and risk factors for placenta-related obstetric complications.&#x0D; Results: APCA (+) and APCA (–) groups showed no statistically significant difference in terms of demographic findings such as age, gravidity, parity, BOI, and the number of miscarriages.. We have demonstrated that 69.2% (9/13) of the APCA (+) cases have two or more skin diseases, while 34% of APCA (-) women have multiple skin diseases. There was a statistically significant difference between APCA (+) and APCA (–) groups in terms of the presence of single or multiple skin diseases (p=0.029). We could not demonstrate a statistically significant difference between APCA (+) and APCA (–) patients in terms of the presence of risk factors for obstetric complications such as immune system problems, MTHFR polymorphisms, hereditary thrombophilia, and diabetes mellitus type-2.&#x0D; Conclusion: APCA positivity which is a risk factor for obstetric complications might be a good indicator used to identify susceptibility to multiple skin disorders during preconception counseling.

Türk çiftlerde infertilite ve metilentetrahidrofolat redüktaz genotipleri arasındaki ilişki

Purpose: Infertility is described as unexplained when all of the tests of a basic infertility evaluation return within normal limits and present in 15% of infertile couples. Some studies indicate that there is an association between methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations and unexplained infertility in male or female grown adults. The objective of this study was to analyze the distributions of MTHFR’s C677T and A1298C genotypes in couples with unexplained fertility problems (UFP) and healthy controls.&#x0D; Materials and Methods: Two common variants C677T and A1298C of the MTHFR gene were screened in infertile couples (n =60 for C677T polymorphism; n=62 for A1298C polymorphism) and controls from the Cukurova region of Turkey. C677T and A1298C mutations in the MTHFR gene were detected by the SNP analysis (Fragment analysis) kit of the multiplex PCR amplification/ligation products. Homocysteine levels (in serum) were determined by the human hcy ELISA kit and folate values were determined by the Beckman coulter Unicel DxI 800 chemiluminescence test kit at the Central Laboratory of Balcali Hospital in Cukurova University.&#x0D; Results: In this study, an association between unexplained infertility and MTHFR C677T polymorphism was not found. However, we found an association between MTHFR A1298C polymorphism and males with UFP (%7) and controls (%19). A statistically significant difference was observed between the infertile and control groups regarding i) the folate and homocysteine values of MTHFR C677T heterozygous individuals; ii) the homocysteine values of the MTHFR C677T normal individuals; iii) the homocysteine values of MTHFR A1298C heterozygous, normal and homozygous individuals; iv) the MTHFR C677T heterozygous and normal individuals; v) the homocysteine values of MTHFR C677T normal individuals; vi) the folate values of the MTHFR A1298C heterozygous and normal individuals.&#x0D; Conclusion: The etiopathogenesis of unexplained infertility remains largely unexplored. However, the relationship of the folate/homocysteine findings with the MTHFR polymorphisms under study is not clear. The results of our study support a relationship between the MTHFR A1298C polymorphism and male fertility problems.

Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein–protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Detection of Mthfr (C667t) and Mthfd (G1958a) Polymorphisms Among Sudanese Women with The Recurrent Miscarriages

Background Recurrent pregnancy loss affects 1 to 5% of women trying to conceive, I t has a significant impact at individual and social level. Methodology case-control study conducted at the research laboratory of the national center of neurological sciences, Khartoum, Sudan. All patients attending Ibrahim Malik teaching hospital and diagnosed with recurrent spontaneous abortion were included as case and healthy women at reproductive age were included as controls. The DNA was isolated by standard phenol chloroform extraction method, The PCR was done by using commercial thermal cycler machine with specific protocol. PCR products were sent for sequencing to Macro gene Europe Laboratory. Results 494 bp of MTHFR(C677T) and 174 bp of MTHFD (rs2236225) (G19581A) alleles were detected after PCR. The PCR result of MTHFR(C677T) shows; 40 (90%) forMTHFR (C677T) allele was positive in the cases and only12 (24 %) were positive for the control group. For MTHFD (G19581A) allele 42 (95%) were positive in the case group and 14 (28%) were positive in the control. When compared between case and control there was highly significant differences. The sequencing results for MTHFR C677; single Base Exchange was found C&gt;T in the case groups, when used the mutation taster software the mutation was predicted. For MTHFD (G1958A) in the case group tow single Base Exchange were found T&gt;A and G&gt;A, the mutation taster software was predicted T&gt;A mutation. Conclusion According to this result the MTHF polymorphisms might become one of the main causes of unexplained diagnosis women with recurrent spontaneous abortion

X-linked genodermatoses from diagnosis to tailored therapy.

Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources. Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses.

The role of MTHFR polymorphisms in the risk of lipedema.

This study examines the role of MTHFR gene polymorphism (rs1801133) in women with lipedema (LIPPY) body composition parameters compared to a control group (CTRL). We carried out a study on a sample of 45 LIPPY and 50 women as a CTRL. Body composition parameters were examined by Dual-energy X-ray Absorptiometry (DXA). A genetic test was performed for the MTHFR polymorphism (rs1801133, 677C>T) using a saliva sample for LIPPY and CTRL groups. Mann-Whitney tests evaluated statistically significant differences between four groups (carriers and non-carriers of the MTHFR polymorphism for LIPPY and CTRL groups) on anthropometric/body composition parameters to identify patterns. LIPPY showed significantly higher (p<0.05) anthropometric parameters (weight, BMI, waist, abdominal, hip circumferences) and lower waist/hip ratio (p<0.05) compared to the CTRL group. The association between the polymorphism alleles related to the rs1801133 MTHFR gene and the body composition values LIPPY carriers (+) showed an increase in fat tissue of legs and fat region of legs percentage, arm's fat mass (g), leg's fat mass (g), and leg's lean mass (g) (p<0.05) compared to CTRL (+). Lean/fat arms and lean/fat legs were lower (p<0.05) in LIPPY (+) than in CTRL (+). In the LIPPY (+), the risk of developing the lipedema disease was 2.85 times higher (OR=2.85; p<0.05; 95% confidence interval = 0.842-8.625) with respect to LIPPY (-) and CTRL. The presence or absence of MTHFR polymorphism offers predictive parameters that could better characterize women with lipedema based on the association between body composition and MTHFR presence.

Association of MTHFR C677T polymorphism with risk of preterm birth in Indian mothers: a case–control study

BackgroundSince MTHFR is the key enzyme in folate metabolism, its reduction can lead to hyperhomocysteinemia, which can have a negative impact on pregnancy outcome. Moreover, MTHFR polymorphism has also been linked with oxidative stress and genotoxicity. Identifying its ethnicity-specific association can help to reduce the incidence of preterm birth (PTB). Material and methods: Age-matched preterm birth mothers (< 37 weeks) and full-term mothers (> 37 weeks) were carefully selected for the study. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method was adopted to analyse MTHFR C677T polymorphism. Oxidative stress (OS) analysis was performed by measuring the levels of antioxidants (superoxide dismutase (SOD) and catalase (CAT)) and OS damage markers (lipid peroxidation (LPO), total protein). Genotoxicity was confirmed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The statistical analysis was performed by Student’s t test, chi-square test, and one-way ANOVA. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs).ResultsThe MTHFR polymorphism showed statistical significance for PTB outcome with CT and TT genotype frequencies at p < 0.01 and p < 0.05, respectively, between cases and controls. Within the PTB categories (extreme-, very-, moderate-PTB), TT genotype showed statistical significance at (p < 0.05), while CT genotype remained insignificant. Also, statistically high oxidative stress and DNA damage were observed in cases compared to controls for all genotypes. Furthermore, the T allele of the MTHFR gene was found to be linked with significantly increased OS and DNA damage on comparison within the groups.ConclusionsThis study confirms the MTHFR C677T polymorphism, oxidative stress, and genotoxicity biomarkers are associated with the PTB outcome. Analysis of these biomarkers during pregnancy can be of clinical significance.

Analysis and evaluation of correlation between DNA polymorphism in the genes MTHFR, PAI-1 and serum creatinine, creatinine clearance and albumin/creatinine ratio in morning urine of patients with type 2 diabetes mellitus and diabetic nephropathy.

Diabetic nephropathy is a major microangiopathic complication of type 2 diabetes and a leading cause of chronic kidney disease (CKD).

Lactoferrin-The Health-Promoting Properties and Contemporary Application with Genetic Aspects.

The aim of the study is to present a review of literature data on lactoferrin's characteristics, applications, and multiple health-promoting properties, with special regard to nutrigenomics and nutrigenetics. The article presents a new approach to food ingredients. Nowadays, lactoferrin is used as an ingredient in food but mainly in pharmaceuticals and cosmetics. In the European Union, bovine lactoferrin has been legally approved for use as a food ingredient since 2012. However, as our research shows, it is not widely used in food production. The major producers of lactoferrin and the few available food products containing it are listed in the article. Due to anti-inflammatory, antibacterial, antiviral, immunomodulatory, antioxidant, and anti-tumour activity, the possibility of lactoferrin use in disease prevention (as a supportive treatment in obesity, diabetes, as well as cardiovascular diseases, including iron deficiency and anaemia) is reported. The possibility of targeted use of lactoferrin is also presented. The use of nutrition genomics, based on the identification of single nucleotide polymorphisms in genes, for example, FTO, PLIN1, TRAP2B, BDNF, SOD2, SLC23A1, LPL, and MTHFR, allows for the effective stratification of people and the selection of the most optimal bioactive nutrients, including lactoferrin, whose bioactive potential cannot be considered without taking into account the group to which they will be given.

Evaluation of homocysteine, folic acid and methylenetetrahydrofolate reductase C677T gene polymorphism associated with recurrent spontaneous miscarriage

This study was aimed to assess the association between evaluation of homocysteine level, folic acid and methylenetetrahydrofolate reductase MTHFR C677T gene polymorphism and recurrent pregnancy loss RSA. Sixty four women diagnosed with RSA and 41 normal fertile female, who had at least one or more child, 21 of them were pregnant women while 20 were non-pregnant. The level of homocysteine was high in women with RSA (11.41+3.75) (p&lt;0.05) compared to normal fertile women either pregnant (7.02+2.13) or non-pregnant (6.84+2.08), low levels of folic acid was observed (6.35+2.09) in women with RSA (p&lt;0.05) compared to fertile women either pregnant(10.08+3.08) or non-pregnant(11.27+3.15). No statistically significant difference was observed in the distribution of genotypes between cases and controls for MTHFR polymorphism. In conclusion, the present study reveals to lack of association of MTHFR C677T polymorphism in RSA women.

Th137Cs radionuclides, folate cycle and physical development of children living near the Chornobyl exclusion zone

The purpose of the study: to assess the impact of incorporated 137Cs radionuclides on the physical development of boys and girls living near the Chornobyl Exclusion Zone, taking into account the state of the folate cycle and the MTHFR:C677T genetic polymorphism. Research methods: іnstrumental, laboratory, mathematical and statistical. Results: Within the framework of international projects, an assessment of physical development was carried out according to the Rohrer index (IR), the levels and relationship of incorporated 137Cs, vitamins B6, B9, B12, homocysteine (Hcy), allelic variants of the MTHFR:C677T genetic polymorphism were determined in 260 children aged 13-17 years old from Ivankivskyi and Polisskyi districts of the Kyiv region, bordering the Chornobyl Exclusion Zone. It has been established that among the surveyed, the more proportion is the subgroup of adolescents with harmonious physical development (respectively, for boys - 70.40%, for girls - 65.93%). It was shown that boys and girls with disharmonious high physical development (respectively 15.20% and 25.19%) contained significantly less 137Cs radionuclides in their bodies, compared with children from the subgroups of harmonious and disharmonious low physical development. In the analyzed groups of boys and girls, an inverse correlation was recorded between the specific activity of 137Cs and the values of anthropometric indicators. The most pronounced inverse relationship between the specific activity of 137Cs and the values of mass, as well as body length and IR, was found in the subgroup of harmoniously developed girls. The subgroup of harmoniously developed boys differed from the subgroup of harmoniously developed girls by a higher specific activity of 137Cs in the body and a higher level of Hcy in the blood. The decrease in the level of Hcy in the blood of harmoniously developed girls, compared with harmoniously developed boys, may be associated with a higher level of vitamin B12 in the blood, as well as with a more intense functioning of the trans-sulfurization cycle. Comparative analysis showed that in the subgroup of girls with overweight, the proportion of cases of carriage of genotypes composed of neutral alleles of the C/C polymorphism MTHFR:677 is greater than in the subgroup of harmoniously developed girls. At the same time, a lower specific activity of 137Cs in their body was registered. It is concluded that incorporated 137Cs radionuclides cause a decrease in body weight in children living in the area affected by the accident at the Chоrnobyl nuclear power plant. At the same time, there is a metabolic disorder, in the form of an increase in the content of Hcy in the blood, more pronounced in boys. The process of incorporation of 137Cs radionuclides into the body of children may be associated with the T allele of the MTHFR:C677 polymorphism, which affects the activity of methylenetetrahydrofolate reductase.

Protective effect of metafolin in pregnant patients with MTHFR polymorphism, under heparin and aspirin protect treatment

Introduction: Thrombophilias during pregnancy are associated with maternal-fetal morbidity and mortality. In addition to this, the physiological changes that arise during pregnancy also generate a state of hypercoagulability, which can lead to complications during pregnancy such as Fetal Growth Restriction (FGR), Preeclampsia and Gestational Loss (GL). The objective was to evaluate the efficacy of Metafolin (MF) against Folic Acid (FA), in pregnant women with MTHFR-C677T mutation. Material and method: Retrospective, observational and cross-sectional study, which included 73 pregnant women. Groups: 1) GAF-T: Treatment with Folic Acid (FA, 400 mcg/24h) and 2) GMf-T: Treatment with Metafolin (Mf, 0.71 g/24h). In all cases, the women had the MTHFR C677T mutation and were treated with Heparin (5000 IU/12h) and Aspirin Protect (100 mg/24h), from the first trimester of pregnancy. Anthropometric data collection (in mothers and their newborns), presence of complications during pregnancy, MTHFR-C677T single nucleotide polymorphism (SNP) study and placental pathology were evaluated. Results: The prevalence of Fetal Growth Restriction (FGR) (15.3 vs 11.1%), placental abruption (PA) (7.6 vs 5.5%), hypertension (7.6 vs 0%) and preeclampsia (7.6 vs 5.5%) in GAF-T and GMf-T was low. GMf-T presented fewer small villi (61.5 vs 22.2%), ischemic changes (76.9 vs 22.2%), erythrocyte extravasation (61.5 vs 22.2%) and hematomas (46.1 vs 11.1%). Conclusion: The application of Mf from the beginning of pregnancy decreases the probability of developing placental pathologies. In addition, the joint application of Heparin and Aspirin Protect reduces the risk of developing complications during pregnancy such as Fetal Growth Restriction (FGR), Placental Abruption (PA), Hypertension and Preeclampsia.

Association of gene polymorphism MTHFR C677T and MTHFR A1298C with atrial fibrillation

Association of gene polymorphism MTHFR C677T and MTHFR A1298C with atrial fibrillation

CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk of a first myocardial infarction with fatal outcome among women.

Cystathionine-gamma-lyase (CSE) in the transsulfuration pathway generates hydrogen sulfide (H2S), suggested regulating cardiovascular function. The G1208T polymorphism in the CTH gene, rs1021737, has, in addition toMTHFR, been found to increase homocysteine, related to myocardial infarction (MI) risk. This study aimed, for the first time, to investigate the associations of the polymorphisms CTH G1208T, MTHFR C677T, and A1298C with the prospective risk of developing a fatal or non-fatal first MI. This case-referent study included 545 cases later developing a first-ever MI and 1,054 referents from the Northern Sweden Health and Disease Study. Fatal MI was defined as death within 28days after MI symptoms. Women, but not men, had a positive association between fatal MI and the CTH G1208T, odds ratio [95% confidence interval] 3.14 [1.16-8.54] for heterozygotes, and the dominant model 3.22 [1.22-8.51], and for the MTHFR A1298C heterozygotes 3.24 [1.26-8.34] and the dominant model 2.63 [1.06-6.50]. The MTHFR C677T polymorphism was not related to MI. This study indicates that the minor alleles of CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk for a fatal MI among women but not for non-fatal MI. No association was found in men.

Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice

A genetic predisposition to hepatic steatosis may be associated with dietary patterns. We hypothesized that a common variant in human methylenetetrahydrofolate reductase (MTHFR 677C→T) was previously associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between the human MTHFR polymorphism and NAFLD using fructose-fed male C57BL/6 Mthfr+/+ and Mthfr+/− mice, a model for the human gene variant. Mice were fed an 8% fructose solution for 12 weeks. Mthfr+/− mice had significantly increased abdominal fat mass and hepatic triglyceride (TG) but displayed a similar liver mass when compared with Mthfr+/+ mice. Liver morphology showed that mild MTHFR deficiency induced liver lipid droplet deposition and inflammatory cell infiltration, suggesting accelerated lipid accumulation in the liver. Moreover, mild MTHFR deficiency increased hepatic xanthine oxidase activity and uric acid accumulation. Using untargeted lipidomics, we identified 116 differentially expressed lipids species in the liver of Mthfr+/− mice when compared with Mthfr+/+ animals. The most significant lipid increase was observed in 47 TGs, followed by 33 phosphatidylcholines in Mthfr+/− mice liver. When compared with Mthfr+/+ liver, 9 TGs were dramatically decreased in Mthfr+/− liver. These changes were associated with upregulated gene expressions related to triglyceride synthesis and storage. Thus, Mthfr+/− mice developed NAFLD disease. These findings suggested the Mthfr variant may be at an increased risk of liver steatosis on a fructose solution diet.

Association of affective disorders and MTHFR, MTR, and MTRR gene polymorphisms: preliminary results of a family study

Genetic polymorphisms associated with impaired one-carbon metabolism (1-CM) can be a risk factor not only for somatic and neurological diseases, but also for affective disorders (AD).Objective: to compare the frequency of genetic polymorphisms MTHFR, MTR, MTRR associated with 1-CM disorders among patients with AD, their blood relatives and healthy individuals.Patients and methods. This cross-sectional study of the frequency of genetic polymorphisms (MTHFR, MTR, MTRR) associated with 1-CM included patients with AD (n=24), their blood relatives (n=40), as well as a group of healthy individuals (n=35). All study participants underwent a structured diagnostic interview, as well as genetic analysis using real-time polymerase chain reaction.Results and discussion. Patients with AD were statistically more likely to carry the minor allele C of the 1298A&gt;C polymorphism of the MTHFR gene and the minor allele G of the 2756A&gt;G polymorphism of the MTR gene compared to the group of healthy individuals. The minor allele T of the 677C&gt;T polymorphism of the MTHFR gene was associated with longer depressive episodes, as well as with the presence of concomitant cardiovascular diseases in blood relatives of patients with AD.Conclusion. Genetic polymorphisms associated with 1-CM may contribute to familial aggregation of AD and somatic diseases. Further highquality family studies using molecular genetic methods are needed.