同: dihydropyrimidine dehydrogenase

WordNet

the 4th letter of the Roman alphabet (同)d

PrepTutorEJDIC

〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥
deuteriumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/18 20:51:06」(JST)

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Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessive^[1] metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

Individuals with this condition may develop life-threatening toxicity following exposure to 5-fluorouracil (5-FU), a chemotherapy drug that is used in the treatment of cancer.^[2]^[3] Beside 5-FU, widely prescribed oral fluoropyrimidine capecitabine (Xeloda) could put DPD-deficient patients at risk of experiencing severe or lethal toxicities as well.^[4]^[5]

Genetics[edit]

Dihydropyrimidine dehydrogenase deficiency has an autosomal recessive pattern of inheritance.

DPD deficiency is inherited in an autosomal recessive manner.^[1] This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Epidemiology[edit]

Current research suggests that nearly 8% of the population has at least partial DPD deficiency. A diagnostics determination test for DPD deficiency is available and it is expected that with a potential 500,000 people in North America using 5-FU this form of testing will increase. The whole genetic events affecting the DPYD gene and possibly impacting on its function are far from being elucidated, and epigenetic regulations could probably play a major role in DPD deficiency.

It is more common among African-Americans than it is among Caucasians.^[6]

References[edit]

^ ^a ^b Diasio RB, Beavers TL, Carpenter JT (Jan 1988). "Familial deficiency of dihydropyrimidine dehydrogenase: biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity" (Free full text). J Clin Invest. 81 (1): 47–51. doi:10.1172/JCI113308. PMC 442471. PMID 3335642.
^ Van Kuilenburg AB (Mar 2006). "Screening for dihydropyrimidine dehydrogenase deficiency: to do or not to do, that's the question". Cancer investigation 24 (2): 215–217. doi:10.1080/07357900500524702. PMID 16537192.
^ Lee A, Ezzeldin H, Fourie J, Diasio R (Aug 2004). "Dihydropyrimidine dehydrogenase deficiency: impact of pharmacogenetics on 5-fluorouracil therapy". Clinical advances in hematology & oncology : H&O 2 (8): 527–532. ISSN 1543-0790. PMID 16163233.
^ Mercier C, Ciccolini J (Nov 2006). "Profiling dihydropyrimidine dehydrogenase deficiency in patients with cancer undergoing 5-fluorouracil/capecitabine therapy". Clinical colorectal cancer 6 (4): 288–296. doi:10.3816/CCC.2006.n.047. ISSN 1533-0028. PMID 17241513.
^ Mercier C, Ciccolini J (Dec 2007). "Severe or lethal toxicities upon capecitabine intake: is DPYD genetic polymorphism the ideal culprit?". Trends in pharmacological sciences 28 (12): 597–598. doi:10.1016/j.tips.2007.09.009. PMID 18001850.
^ Saif MW, Seller S, Diasio RB (Mar 2008). "Atypical toxicity associated with 5-Fluororacil in a DPD-deficient patient with pancreatic cancer. Is ethnicity a risk factor?". JOP 9 (2): 226–9. PMID 18326935.

External links[edit]

Site dedicated exclusively to DPD Deficiency and Fluorouracil (5-FU) Toxicity related issues - dpd-deficiency.com
Dihydropyrimidine dehydrogenase deficiency at NIH's Office of Rare Diseases

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English Journal

5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases.

Cordier PY, Nau A, Ciccolini J, Oliver M, Mercier C, Lacarelle B, Peytel E.SourceHopital d'Instruction des Armees Laveran, Marseille, France. pierre-yves.cordier@laposte.net
Cancer chemotherapy and pharmacology.Cancer Chemother Pharmacol.2011 Sep;68(3):823-6. Epub 2011 May 8.
PURPOSE: 5-Fluorouracil (5-FU) is a mainstay for treating various solid tumours in adults, including digestive and head and neck cancers. 5-FU-related toxicities usually include haematological, digestive and cutaneous features. Additionally, 5-FU has been described as being potentially neurotoxic in
PMID 21553285

Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation.

Hie M, Iitsuka N, Otsuka T, Tsukamoto I.SourceDepartment of Food Science and Nutrition, Nara Women's University, Kitauoya-Νishimachi, Nara 630-8506, Japan.
International journal of molecular medicine.Int J Mol Med.2011 Sep;28(3):455-62. doi: 10.3892/ijmm.2011.697. Epub 2011 May 11.
Insulin-dependent diabetes mellitus (IDDM) is known to be associated with an increased risk of osteopenia. However, the cellular and molecular mechanisms for IDDM-induced alterations of the bone are not well understood. The effects of IDDM on bone metabolism were investigated using rats rendered dia
PMID 21567076

Japanese Journal

Effects of Ovariectomy on Bone Metabolism and Bone Mineral Density in Spontaneously Diabetic Torii-Leprfa Rats

KIMURA Shuichi,SASASE Tomohiko,OHTA Takeshi,MATSUSHITA Mutsuyoshi
日本獣醫學会会誌 73(8), 1025-1029, 2011
… However, it is not known whether diabetes and estrogen deficiency can lead to bone abnormalities in the female SDT-<i>fa/fa</i> … Serum osteocalcin, a bone formation marker, and urine deoxypyridinoline (DPD), a bone resorption marker, were sequentially analyzed before and at 5, 15 and 30 weeks after OVX. … Serum osteocalcin and urine DPD levels were lower in SDT-<i>fa/fa</i> …
NAID 130000677050

Children's toxicology from bench to bed - Liver Injury (1) : Drug-induced metabolic disturbance : Toxicity of 5-FU for pyrimidine metabolic disorders and pivalic acid for carnitine metabolism

Ito Tetsuya
Journal of toxicological sciences 34(Special Issue II), SP217-SP222, 2009-07
… Congenital disorders of metabolism show a wide spectrum of symptoms as a consequence of impairment of a certain metabolic pathway by mutated enzymes resulting in abnormal accumulation of enzyme substrates, deficiency of expected products, and abnormal burden to collateral metabolic pathways, etc. …
NAID 110007337718