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Query: UMLS:C0042963 (
vomiting
)
31,883
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The authors investigated whether high-dose methotrexate-induced toxicity differed according to the presence of
methylenetetrahydrofolate reductase
(
MTHFR
) or reduced folate carrier 1 (RFC1) genetic polymorphism. The authors studied 15 children with acute lymphoblastic leukemia or lymphoblastic lymphoma who were treated using protocols that included high-dose methotrexate (3.0 g/m), for an overall total of 43 courses. Methotrexate-induced toxicities and the plasma methotrexate concentrations were evaluated retrospectively. Hematologic toxicity was the most frequently observed toxicity, appearing in 87% of the patients. In a subset of patients (47%), elevation of liver transaminase levels showed a repeated tendency to develop. High plasma methotrexate concentrations at 48 hours after the methotrexate infusion were not significantly related to methotrexate-induced toxicities except for mucositis. A generalized estimating equation analysis revealed that
vomiting
during the high-dose methotrexate treatment was more pronounced in patients who had a larger number of G alleles at the RFC1 80G>A polymorphism. No significant differences in the development of other toxicities or in the plasma methotrexate concentrations were observed for the different
MTHFR
677C>T or RFC1 80G>A polymorphisms. This study suggests but does not prove that the RFC1 80G>A polymorphism may contribute to interindividual variability in responses to high-dose methotrexate.
...
PMID:Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma. 1646 75
We describe the case of a previously healthy young man who presented with headache, diplopia, nausea,
vomiting
, and bilateral papilledema. Magnetic resonance venography of the brain revealed thrombosis of the right transverse sinus. Blood tests showed elevated homocysteine levels, and coagulation studies revealed a homozygous C677T mutation and a heterozygous A1298C mutation of the
methylenetetrahydrofolate reductase
(
MTHFR
) gene. The patient had no other etiology for venous thrombosis. We recommend screening patients who present with sinus thrombosis for
MTHFR
gene mutations.
...
PMID:Bilateral transverse sinus thrombosis secondary to a homozygous C677T MTHFR gene mutation. 1866 57
Migraine is a common neurological disorder and is characterized by debilitating head pain and an assortment of additional symptoms which can include nausea,
emesis
, photophobia, phonophobia, and occasionally, visual sensory disturbances. A number of genes have been implicated in the pathogenesis of this disease, including genes involved in regulating the vascular system. Of particular importance are the
methylenetetrahydrofolate reductase
(
MTHFR
) gene and the role it plays in migraine with aura. Migraine with aura has previously been shown to have a significant comorbidity with stroke, making the vascular class of genes a priority for migraine studies. In this report, we outline the importance of the
MTHFR
gene in migraine and also discuss the use of a genetic isolate to investigate
MTHFR
genetic variants. From this study, 3
MTHFR
single nucleotide polymorphisms showing association with migraine in the Norfolk Island population have been identified, thus reinforcing the potential role of
MTHFR
in migraine susceptibility. Further studies will continue to build a gene profile of variants involved in the complex disease migraine and improve understanding of the underlying genetic causes of this disorder.
...
PMID:The role of the MTHFR gene in migraine. 2294 35
Introduction:
High dose methotrexate (HD-Mtx) is highly effective and significantly improves overall acute lymphoblastic leukemia (ALL) patients survival. The pharmacodynamics of Mtx depends on the polymorphism of genes encoding proteins engaged in the folate metabolism pathway. The aim of the current study is to determine the relationship between variants of folate metabolism-related genes and the frequency of acute toxicities of HD-Mtx.
Material and Methods:
A group of 133 patients aged 1.5-18.1 years (median: 6.3) was treated in accordance with the ALL-IC-2002 and ALL-IC-2009 protocols. The following polymorphisms were determined: 80 G>A
SLC19A1
(solute carrier family 19 member 1; rs1051266) with direct DNA sequencing, as well as 677 C>T
MTHFR
(
methylenetetrahydrofolate reductase
; rs1801133) and the tandem repeats of the
TS
(thymidylate synthase) with PCR technique. HD-Mtx organ toxicities were evaluated based on the laboratory tests results and the National Cancer Institute criteria.
Results:
In patients with genotypes AA for
SLC19A1
and CC or CT for
MTHFR
Mtx steady state concentrations (C
ss
) and AUC
inf
were distinctly higher. In patients with genotype 3R/3R for
TS
initial elimination rate constant was significantly higher (
P
= 0.003). Patients receiving Mtx at the dose of 5 g/m
2
had lower clearance (4.35 vs. 8.92 L/h/m
2
) as compared to the ones receiving 2 g/m
2
that indicates non-linear Mtx elimination at the higher dose. Liver impairment was the most frequently observed toxicity. The homozygous genotype was associated with a significantly higher incidence of hepatic toxicity for both the
SLC19A1
(
P
= 0.037) and
TS
(
P
= 0.002). Logistic regression analysis indicated an increased risk of
vomiting
for the 2R/3R genotype of the
TS
gene (OR 3.20, 95% CI 1.33-7.68,
P
= 0.009) and for
vomiting
and hepatic toxicity for the 3R/3R genotype (
vomiting
: OR 3.39, 95% CI 1.12-10.23,
P
= 0.031; liver toxicity: OR 2.28, 95% CI 1.05-4.95,
P
= 0.038). None of the acute toxicities differed between the analyzed dosing groups.
Conclusions:
Determination of polymorphisms of
SLC19A1, MTHFR
, and
TS
genes might allow for a better prior selection of patients with higher risk of elevated Mtx levels. Our study is the first one to report the increased risk of hepatotoxicity and
vomiting
in patients with
TS
polymorphisms.
...
PMID:Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate. 3261 64
Homocysteine remethylation disorders are rare inherited disorders caused by a deficient activity of the enzymes involved in the remethylation of homocysteine to methionine. The adolescent/adult-onset remethylation disorders are rarely reported. We analyzed the clinical and genetic characteristics of seven cases with adolescent/adult remethylation disorders, including 5 cases of the cobalamin C disease (cblC) and 2 cases of the
methylenetetrahydrofolate reductase
deficiency. The average onset age was 21.1 (range 14 to 40) years. All patients complained of gait disturbances. Other common symptoms included psychiatric symptoms (5/7) and cognitive decline (4/7). Acute encephalopathy, dysarthria, anorexia,
vomiting
, ketoacidosis, anemia, cataract, and hand tremor were also observed. The mean total homocysteine in serum when the patients were diagnosed was 94.6 (range 53.1-154.5) mol/L. Electrophysiological studies revealed neuropathy in the lower limbs (6/7). The brain MRI showed reversible altered signal from the dorsal portions of the cerebellar hemispheres (1/7), periventricular hyperintensity (2/7), and delayed/impaired myelination (2/7). The sural nerve biopsy performed in one case showed a modest loss of myelinated fibers. Five patients showed heterozygous mutations of the MMACHC gene, including c.482G>A (5/5), c.609G>A (2/5), and c.658-660delAAG (3/5). Two patients showed heterozygous mutations of the MTHFR gene, including c.698C>A (2/2), c.698C>G (1/2), and c.236+1G>A (1/2). The patients responded well to the treatments with significant improvements. Adolescent/adult-onset remethylation disorders are easily misdiagnosed. We recommend testing the serum homocysteine concentrations in young/adult patients with unexplained neuro-psychotic symptoms. Furthermore, individuals with significantly elevated serum homocysteine concentrations should be further tested by organic acid screening and genetic analysis.
...
PMID:Adolescent/adult-onset homocysteine remethylation disorders characterized by gait disturbance with/without psychiatric symptoms and cognitive decline: a series of seven cases. 3300 Mar 30
