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

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.

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Association Between MTHFR 677C>T Polymorphism and Vitamin B12 Deficiency: A Case-Control Study

Journal of Medical Biochemistry ◽

10.1515/jomb-2017-0051 ◽

2018 ◽

Vol 37 (2) ◽

pp. 141-147 ◽

Cited By ~ 3

Author(s):

Khalid M. Al-Batayneh ◽

Mazhar Salim Al Zoubi ◽

Murad Shehab ◽

Bahaa Al-Trad ◽

Khaldon Bodoor ◽

...

Keyword(s):

Vitamin B12 ◽

Case Control Study ◽

Vitamin B12 Deficiency ◽

Case Control ◽

Health Concern ◽

Cobalamin Deficiency ◽

Mthfr Polymorphisms ◽

Jordanian Population ◽

B12 Deficiency ◽

Control Study

SummaryBackground:Vitamin B12 (cobalamin) deficiency is a prevalent worldwide health concern. Several factors are associated with vitamin B12 deficiency including lifestyle, genetic predisposition, and malfunctions in the absorption and transport of vitamin B12. In the current case-control study, we aimed at investigating the association between MTHFR polymorphisms and vitamin B12 deficiency in a Jordanian population.Methods:Two polymorphic sites of the MTHFR gene (c.677C>T, rs1801133 and c.1286A>C, rs1801131) were analyzed using RFLP and DNA sequencing in a group of vitamin B12 deficient individuals (45 males and 55 females). As a control, 100 matching individuals (age and sex) with vitamin B12 levels > 200 ng/mL were also recruited for this study.Results:The MTHFR c.677C>T variant was significantly associated with vitamin B12 deficiency in individuals from northern Jordan. The frequency of the homozygous MTHFR c.677C>T genotype was significantly higher in B12 deficient individuals in comparison with the control group (X2= 8.397, p = 0.0150). The T allele frequency showed significant association with vitamin B12 deficiency in the study population (OR= 1.684, 95% CI: 1.116 to 2.542, p = 0.017). On the other hand, the MTHFR c.1286A>C variant did not show significant association with vitamin B12 deficiency in the selected population.Conclusions:Our results showed a significant association between homozygous MTHFR c.677C>T variant and T allele frequencies and vitamin B12 deficiency in the Jordanian population.

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Homologous G776G Variant of Transcobalamin-II Gene is Linked to Vitamin B12 Deficiency

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000536 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 151-155

Author(s):

Khalid M. Al-Batayneh ◽

Mazhar Salim Al Zoubi ◽

Bahaa Al-Trad ◽

Emad Hussein ◽

Wesam Al Khateeb ◽

...

Keyword(s):

Vitamin B12 ◽

Megaloblastic Anemia ◽

Intrinsic Factor ◽

Vitamin B12 Deficiency ◽

Intermediate Phenotype ◽

Cobalamin Deficiency ◽

Control Group ◽

Jordanian Population ◽

B12 Deficiency ◽

Transcobalamin Ii

Abstract. Vitamin B12 (Cobalamin) deficiency, due to improper internalization of cobalamin, is a metabolic disorder prevalent in impoverished and elderly populations and is associated with megaloblastic anemia and dementia. It has been suggested that mutations in transcobalamin II ( TCN2) or gastric intrinsic factor (GIF) proteins can alter their binding efficiency to cobalamin or reduce the ability of their receptors to internalize them. In this case-control study, the correlation between vitamin B12 deficiency and alternative alleles of TCN2 and GIF was investigated in a Jordanian population. One hundred individuals with vitamin B12 deficiency (B12 < 200 mg/mL) were enrolled in our study to evaluate the TCN2 and GIF polymorphisms. The control group (B12 > 200 mg/mL) included 100 individuals. Our results indicated a significant association between the homologous variant of the TCN2 gene (G776G) and vitamin B12 deficiency, and an intermediate phenotype in heterozygous individuals ( p < 0.001, OR = 5.6, 95% CI = 2.95 to 10.63). The GIF gene, however, showed no correlation between the A68G variant and vitamin B12 deficiency ( p = 0.2). This study expounds the association of TCN2 polymorphism with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2 and GIF genes polymorphisms on vitamin B12 deficiency and associated disorders.

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The impact of vitamin B12 deficiency on infant gut microbiota

European Journal of Pediatrics ◽

10.1007/s00431-019-03517-2 ◽

2019 ◽

Vol 179 (3) ◽

pp. 385-393 ◽

Cited By ~ 2

Author(s):

Perran Boran ◽

Hatice Ezgi Baris ◽

Eda Kepenekli ◽

Can Erzik ◽

Ahmet Soysal ◽

...

Keyword(s):

Gut Microbiota ◽

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

B12 Deficiency ◽

The Impact

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Vitamin B12 deficiency: metabolic effects, clinical evaluation, and treatment

Revista de Medicina da UFC ◽

10.20513/2447-6595.2019v59n2p40-49 ◽

2019 ◽

Vol 59 (2) ◽

pp. 40 ◽

Cited By ~ 1

Author(s):

Synara Cavalcante Lopes ◽

Daniel Duarte Gadelha ◽

Manuela Dias de Carvalho ◽

Virgínia Oliveira Fernandes ◽

Renan Magalhães Montenegro Junior

Keyword(s):

Insulin Resistance ◽

Vitamin B12 ◽

Neurological Disorders ◽

Vitamin B12 Deficiency ◽

The Body ◽

Water Soluble ◽

Metabolic Effects ◽

Pharmacological Treatments ◽

B12 Deficiency ◽

Composition Changes

Vitamin B12 is a water-soluble essential micronutrient, required by all the body cells. Its deficiency has been implicated not only in hematological and neurological disorders, but also in many metabolic processes, such as insulin resistance and body composition changes, which have aroused particular interest in recent years. This study reviews the physiology of vitamin B12 from its digestion and absorption to its distribution in tissues, metabolic effects and controversies regarding the diagnosis of deficiency, and to dietary and pharmacological treatments.

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RELATIONSHIP OF MATERNAL VITAMIN B12 STATUS IN PREGNANCY WITH PRETERM BIRTH AND MATERNAL HEALTH RISKS

International Medical Journal ◽

10.37436/2308-5274-2020-2-7 ◽

2020 ◽

pp. 32-38

Author(s):

VICTORIA LAZAROVA SPASOVA ◽

LILIA IVANOVA KOLEVA ◽

MARIETA ANTONOVA POPOVA ◽

VALENTINA BOYANOVA PETKOVA ◽

MILEN VENTZISLAVOV DIMITROV

Keyword(s):

Preterm Birth ◽

Vitamin B12 ◽

Pregnant Women ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Inverse Association ◽

Maternal Vitamin ◽

B12 Deficiency ◽

The Impact ◽

In Pregnancy

Vitamin B12 is known to be vital for cell growth and population during pregnancy. This retrospective and prospective case−control study was aimed to disclose a health risk for pregnant women with vitamin B12 deficiency, as well as the one of the preterm birth. The main tasks set and performed in this research were as follows: to compare the obstetrics anamnesis between the women who gave birth on term and women who gave birth before term; to find the prevalence of vitamin B12 insufficiency in pregnancy; to determine its association with preterm birth and low birth weight; to examine its association with spontaneous abortions, and to investigate its relationship with obesity and hemoglobin levels in pregnant women. The conducted investigation involved 107 women who gave birth before the 37th week of gestation and 101 women who gave birth after the 37th week of gestation at the outpatient clinic of the University Hospital "Maichin Dom" in Bulgaria. Our study revealed a correlation between maternal vitamin B12 deficiency, overweight and low hemoglobin level. Our results showed no significant correlation between serum vitamin B12 level and the risk of preterm birth. However, we found an inverse association between vitamin B12 level and overweight before pregnancy and at the time of giving birth. As well there was confirmed the strong connection between meat consumption and vitamin B12 level. The paper emphasizes that the deficiency of the vitamin occurs most likely in the women with inadequate diets. Such a deficiency is actually confirmed to have serious health consequences for pregnant women and their offspring. Therefore further profound and numerous studies should be performed to properly assess the correlation between vitamin B12 and preterm birth, as well as to understand better the impact of vitamin B12 over pregnant women. Key words: vitamin B12, preterm birth, pregnancy, overweight, hemoglobin.

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Biochemical Impedance on Intracellular Functions of Vitamin B12 in Chronic Toxigenic Mold Exposures

The Scientific World JOURNAL ◽

10.1100/tsw.2007.113 ◽

2007 ◽

Vol 7 ◽

pp. 1649-1657 ◽

Cited By ~ 1

Author(s):

Ebere C. Anyanwu ◽

Ijeoma Kanu

Keyword(s):

Vitamin B12 ◽

Neurological Disorders ◽

Vitamin B12 Deficiency ◽

Methionine Synthase ◽

Neurological Manifestations ◽

Biochemical Processes ◽

B12 Deficiency ◽

Spinal Degeneration ◽

One Carbon Metabolism ◽

And Function

A majority of patients with neurological disorders with chronic exposures to toxigenic molds and mycotoxins has vitamin B12 deficiency that is unrelated to dietary insufficiency. Vitamin B12 is a source of coenzymes, and participates in intracellular recycling of methionine, and in methionine synthase reactions. The biochemical processes that lead to B12 depletion and deficiency are not fully understood. This paper examines and assesses various most likely biochemical reasons that could impede upon the normal intracellular functions of vitamin B12 that lead to neurological manifestations. By biochemical implications and derivations, it is most likely that mycotoxins interrupt the structure and function of vitamin B12 through reactive interference with the normal One-Carbon metabolism leading to the observed clinical neurological manifestations such as nerve damage and, demyelination, degeneration of PNS leading to paralysis, progressive peripheral neuropathy, and spinal degeneration.

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Low vitamin B12 diet increases liver homocysteine levels and leads to liver steatosis in rats

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2019.v38.194-201 ◽

2019 ◽

Vol 38 (3) ◽

pp. 194

Author(s):

Imelda Rosalyn Sianipar ◽

Irena Ujianti ◽

Sophie Yolanda ◽

Ahmad Aulia Jusuf ◽

Neng Tine Kartinah ◽

...

Keyword(s):

Insulin Resistance ◽

Vitamin B12 ◽

Insulin Signaling ◽

Liver Steatosis ◽

Vitamin B12 Deficiency ◽

Dietary Vitamin ◽

Control Group ◽

Treatment Groups ◽

Treatment Standard ◽

B12 Deficiency

Background Nonalcoholic fatty liver disease (NAFLD) is one of the most widespread chronic liver diseases, caused by the development of insulin resistance. One of the mechanisms involved is a disturbance in insulin signaling by certain toxic substances that interact with one of the proteins responsible for the insulin signaling pathway. Increased homocysteine level, upon disruption of the methionine pathway, is associated with insulin resistance. The aim of this study was to evaluate the effect of hyperhomocysteinemia and insulin resistance (HOMA-IR level) induced by dietary vitamin B12 restriction on liver steatosis. Methods A study of laboratory experimental design was conducted involving 18 male Sprague Dawley rats (age 36-40 weeks, BW 300-350 g), that were randomly divided into 3 groups: control, 8-week treatment, and 16-week treatment. Standard AIN-93 diet was administered to the control group, whereas rats in the treatment groups were fed vitamin B12 deficiency-AIN-93M. At the end of treatment, liver homocysteine levels were determined by ELISA, HOMA-IR values were calculated, and steatosis degree of the liver was determined histologically. Statistical analysis was performed using independent t-test. Results A significant increase in liver homocysteine levels was found between the control and both the 8- and 16-week treatment groups (p<0.001). HOMA-IR levels were significantly higher in both treatment groups compared to controls (p<0.001). The area of liver steatosis in both treatment groups was significantly larger than that of the control group (p<0.001). Conclusion Increased homocysteine levels due to dietary vitamin B12 deficiency induces liver steatosis due to insulin resistance in rats.

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Cobalamin and Folate Evaluation: Measurement of Methylmalonic Acid and Homocysteine vs Vitamin B12 and Folate

Clinical Chemistry ◽

10.1093/clinchem/46.8.1277 ◽

2000 ◽

Vol 46 (8) ◽

pp. 1277-1283 ◽

Cited By ~ 217

Author(s):

George G Klee

Keyword(s):

Vitamin B12 ◽

Methylmalonic Acid ◽

Megaloblastic Anemia ◽

Significant Risk ◽

Vitamin B12 Deficiency ◽

Significant Risk Factor ◽

Nerve Degeneration ◽

Early Evaluation ◽

B12 Deficiency ◽

The Impact

Abstract Vitamin B12 and folate are two vitamins that have interdependent roles in nucleic acid synthesis. Deficiencies of either vitamin can cause megaloblastic anemia; however, inappropriate treatment of B12 deficiency with folate can cause irreversible nerve degeneration. Inadequate folate nutrition during early pregnancy can cause neural tube defects in the developing fetus. In addition, folate and vitamin B12 deficiency and the compensatory increase in homocysteine are a significant risk factor for cardiovascular disease. Laboratory support for the diagnosis and management of these multiple clinical entities is controversial and somewhat problematic. Automated ligand binding measurements of vitamin B12 and folate are easiest to perform and widely used. Unfortunately, these tests are not the most sensitive indicators of disease. Measurement of red cell folate is less dependent on dietary fluctuations, but these measurements may not be reliable. Homocysteine and methylmalonic acid are better metabolic indicators of deficiencies at the tissue level. There are no “gold standards” for the diagnosis of these disorders, and controversy exists regarding the best diagnostic approach. Healthcare strategies that consider the impact of laboratory tests on the overall costs and quality of care should consider the advantages of including methylmalonic acid and homocysteine in the early evaluation of patients with suspected deficiencies of vitamin B12 and folate.

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Optimized treatment of patients with alcoholic steatohepatitis taking into account comorbid anaemic conditions and H.pylori contamination

Bukovinian Medical Herald ◽

10.24061/2413-0737.xxv.3.99.2021.1 ◽

2021 ◽

Vol 25 (3 (99)) ◽

pp. 3-11

Author(s):

T. Antofiichuk ◽

O. Khukhlina ◽

M. Antofiichuk

Keyword(s):

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

Control Group ◽

Control Groups ◽

Alcoholic Steatohepatitis ◽

Clinical Syndromes ◽

B12 Deficiency ◽

H Pylori ◽

Optimized Treatment ◽

And Control

The prospective study of patients with alcoholic steatohepatitis (ASH) showed that 40 % of patients with ASH were diagnosed with anaemic conditions (AC), among which vitamin B12-deficiency anaemia was registered - in 17.5% of cases, anaemia of chronic disease (ACD) – in 10.0% of cases and hemolytic anemia (HA) - in 12.5% of cases. In patients with SH of mixed (including alcoholic) etiology AC was found in 32.0%: vitamin B12 - deficient - in 16.0%, ACD - in 8.0% and hemolytic - in 8.0 % of patients. In patients with ASH, H. pylori contamination was present in 32 (80.0%) individuals, including 100% of patients with B12-deficient anaemia. Among patients with SH of mixed (including alcoholic) etiology, H. pylori was detected in 100.0% of people with AS. The use of Hepadif in the complex therapy of ASH contributed to the elimination or reduction of the intensity of the main clinical syndromes (astheno-vegetative, dyspeptic, cholestatic, hepato-, splenomegaly, hepatic steatosis) and biochemical syndromes (mesenchymal-inflammatory cholestasis, hepatocellular insufficiency), in the range of 1.3-4.3 times (p <0.05), as well as higher efficiency of treatment of patients with ASH with anaemic syndrome in 6.0 times (p <0.05). The efficiency of eradication of H. pylori in the main and control groups accompanied by the use of the 3-component programme of the first line according to the stool test was the same (85.7% and 84.2% (p> 0.05), respectively), but in 57.9 % of patients in the control group, the symptoms of dyspepsia increased or appeared on the background of antibacterial therapy, while no side effects of the drug were found during the study in the main group.

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