ABCC8 p.Cys677Thr
| Predicted by SNAP2: | A: N (72%), D: N (53%), E: N (66%), F: N (87%), G: N (57%), H: N (82%), I: N (93%), K: N (66%), L: N (87%), M: N (72%), N: N (72%), P: N (61%), Q: N (78%), R: N (66%), S: N (82%), T: N (78%), V: N (93%), W: N (61%), Y: N (93%), |
| Predicted by PROVEAN: | A: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] [Portal vein thrombosis]. Gastroenterol Clin Biol. 2006 Oct;30(10):1170-6. Condat B
[Portal vein thrombosis].
Gastroenterol Clin Biol. 2006 Oct;30(10):1170-6., [PMID:17075472]
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No. Sentence Comment
88 Affections acquises Affections génétiques Facteurs de risque de thrombose Syndromes myéloprolifératifs Mutation du gène du Facteur II Contraceptifs oraux Syndrome des antiphospholipides Facteur V Leiden Grossesse Hémoglobinurie paroxystique nocturne Déficit en protéine C Hyperhomocystéinémie Déficit en protéine S Augmentation du Facteur VIII Déficit en protéine Antithrombine III Afibrinogénémie C677T Methyl tetrahydrofolate reductase polymorphism Sarcoïdose Maladie de Behcet •••••••••••••••••••• •••••••••••••••••••• suspectée par l`histoire antérieure.
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ABCC8 p.Cys677Thr 17075472:88:478
status: NEW[hide] Hyperhomocysteinaemia, folate and vitamin B12 in u... Nephrol Dial Transplant. 2002 Mar;17(3):455-61. Billion S, Tribout B, Cadet E, Queinnec C, Rochette J, Wheatley P, Bataille P
Hyperhomocysteinaemia, folate and vitamin B12 in unsupplemented haemodialysis patients: effect of oral therapy with folic acid and vitamin B12.
Nephrol Dial Transplant. 2002 Mar;17(3):455-61., [PMID:11865092]
Abstract [show]
BACKGROUND: Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition). B-complex vitamin supplements have been shown to lower plasma total homocysteine (tHcy) concentrations, but the respective effectiveness of folate and oral vitamin B12 is not yet known. Our objectives were: (i) to determine the status of folate and vitamin B12 in a cohort of unsupplemented dialysis patients (ii) to assess the homocysteine-lowering effect of a folate supplement and then of a folate supplement with added vitamin B12. The responses were analysed for the C677T genotypes of MTHFR. METHODS: Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC). All patients were then given daily supplements of 15 mg of folic acid for 2 months. They were given daily supplements of 1 mg of vitamin B12 in addition to the folate supplements for a further 2 months. Plasma tHcy, folate and vitamin B12 were monitored after each intervention. RESULTS: At baseline folate and vitamin B12 deficiencies were found in 10% and 6% of the patients. Initial plasma tHcy concentrations were high in all patients (mean 38.1+/-15 micromol/l). CC patients tended to have a lower tHcy concentration than pooled CT and TT patients. After 2 months of folate therapy, tHcy concentration decreased significantly to 20.2+/-7 micromol/l (P<0.001) and no significant differences were observed between the different genotype subgroups (19.4+/-6 for CC, 21.3+/-8 for CT, 18.5+/-4 for TT). A significant positive relationship was found between the reduction of tHcy and its initial value (rho=0.615, P<0.0001). The impact of the added vitamin B12 was negligible since tHcy concentrations did not change for the patients as a whole (19.8+/-7 micromol/l, NS) or in any subgroup (19.1+/-5 for CC, 20.3+/-9 for CT and 20+/-7 micromol/l for TT). CONCLUSIONS: (i) Folate and vitamin B12 deficiencies were observed in 10% and 6% respectively of our unsupplemented dialysis patients. (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups. (iii) Vitamin B12 supplements are useful in folate treated patients to prevent cobalamin deficiency and its neurological consequences but they did not lower tHcy plasma levels for the patients as a group or for any of the MTHFR subgroups.
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No. Sentence Comment
1 Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition).
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ABCC8 p.Cys677Thr 11865092:1:214
status: NEW4 The responses were analysed for the C677T genotypes of MTHFR.
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ABCC8 p.Cys677Thr 11865092:4:36
status: NEW6 Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC).
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ABCC8 p.Cys677Thr 11865092:6:97
status: NEW19 (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups.
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ABCC8 p.Cys677Thr 11865092:19:116
status: NEW69 The C677T polymorphic site was determined by PCR amplification followed by restriction-enzyme digestion of the products and analysed on 2% agarose gels w13x.
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ABCC8 p.Cys677Thr 11865092:69:4
status: NEW75 Results Table 1 shows the genotypic distribution of the (C677T) MTHFR mutation and the main characteristics of patients in the different genotype groups.
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ABCC8 p.Cys677Thr 11865092:75:57
status: NEW[hide] Distribution of TYMS, MTHFR, p53 and MDR1 gene pol... Cancer Epidemiol. 2010 Oct;34(5):634-8. Epub 2010 Jul 17. Henriquez-Hernandez LA, Murias-Rosales A, Gonzalez-Hernandez A, de Leon AC, Diaz-Chico N, Fernandez-Perez L
Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy.
Cancer Epidemiol. 2010 Oct;34(5):634-8. Epub 2010 Jul 17., [PMID:20638924]
Abstract [show]
PURPOSE: To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48. MTHFR allele T and p53 allele Pro were strongly associated with toxicity due to chemotherapy (odds ratio, 7.1 (95% confidence interval, 1.4-36.1; p=0.018) and 7.0 (95% confidence interval, 1.2-40.5; p=0.029), respectively). CONCLUSION: We introduced new data related to the contribution of p53 codon 72 to toxicity due to 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy in patients with breast cancer.
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13 Two linked no synonymous SNPs, C677T and A1298C, have been shown to alter enzyme activity and possibly 5-FU sensitivity [9,10].
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ABCC8 p.Cys677Thr 20638924:13:31
status: NEW14 MTHFR C677T has been implicated in different adverse reactions [11].
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ABCC8 p.Cys677Thr 20638924:14:6
status: NEW17 Mutations in the p53 gene are the most common genetic alterations in human Cancer Epidemiology 34 (2010) 634-638 A R T I C L E I N F O Article history: Accepted 20 June 2010 Available online 17 July 2010 Keywords: Breast cancer Neoadjuvant chemotherapy Toxicity Adverse reaction Polymorphism MTHFR p53 A B S T R A C T Purpose To investigate the role of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms in breast cancer patients treated with 5-fluorouracil and cyclophosphamide-based neoadjuvant chemotherapy.
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ABCC8 p.Cys677Thr 20638924:17:366
status: NEW18 Results Observed allelic frequencies were: TSER, (2) 0.54 and (3) 0.46; MTHFR C677T, (C) 0.59 and (T) 0.41; p53 Arg72Pro, (Arg) 0.73 and (Pro) 0.27; MDR1 C3435T, (C) 0.52 and (T) 0.48.
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ABCC8 p.Cys677Thr 20638924:18:78
status: NEW35 Because these gene polymorphisms have been proposed as important factors in chemotherapy response, toxicity and outcome; and considering all these background and observations, we studied the distribution of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms in BC patients from Gran Canaria treated with neoadjuvant chemotherapy.
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ABCC8 p.Cys677Thr 20638924:35:219
status: NEW64 Genotyping Polymorphic sites in TYMS (TSER), MTHFR (C677T), p53 codon 72 (Arg/Pro) and MDR1 (C3435T) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis as previously reported [26].
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ABCC8 p.Cys677Thr 20638924:64:52
status: NEW78 TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T allelic and genotypic frequencies were estimated (Table 3).
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ABCC8 p.Cys677Thr 20638924:78:12
status: NEW79 Observed allelic frequencies were (%): TSER, (2) 54 and (3) 46; MTHFR C677T, (C) 59 and (T) 41; p53 Arg72Pro, (Arg) 73 and (Pro) 27; MDR1 C3435T, (C) 52 and (T) 48.
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ABCC8 p.Cys677Thr 20638924:79:70
status: NEW90 In univariate analysis, a significant association between adverse reactions and the polymorphisms MTHFR C677T and p53 codon 72 was established (Table 4).
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ABCC8 p.Cys677Thr 20638924:90:104
status: NEW100 n Genotypes (n, %) Alleles (n, %) TS 28bp STR 2/2 2/3 3/3 2 3 49 15 (31) 23 (47) 11 (22) 53 (54) 45 (46) MTHFR C677T C/C C/T T/T C T 50 16 (32) 27 (54) 7 (14) 59 (59) 41 (41) p53 codon72 Arg/Arg Arg/Pro Pro/Pro Arg Pro 50 26 (52) 21 (42) 3 (6) 73 (73) 27 (27) MDR1 C3435T C/C C/T T/T C T 50 14 (28) 24 (48) 12 (24) 52 (52) 48 (48) L.A. Henrı´quez-Herna´ndez et al. / Cancer Epidemiology 34 (2010) 634-638636 isms in toxicity due to chemotherapy.
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ABCC8 p.Cys677Thr 20638924:100:111
status: NEW103 Discussion We explored the distribution of TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T gene polymorphisms in breast cancer patients treated with neoadjuvant chemotherapy.
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ABCC8 p.Cys677Thr 20638924:103:55
status: NEW104 The appearance of adverse reactions was significantly associated with the polymorphisms MTHFR C677T and p53 codon 72.
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ABCC8 p.Cys677Thr 20638924:104:94
status: NEW114 MTHFR C677T has been shown to alter enzyme activity as well as 5-FU and MTX sensitivity [9,29].
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ABCC8 p.Cys677Thr 20638924:114:6
status: NEW117 MTHFR C677T polymorphism appears to be an important predictor of CMF-related severe toxicity.
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ABCC8 p.Cys677Thr 20638924:117:6
status: NEW119 The C/C genotype of the MTHFR C677T polymorphism was protective against grade 3-4 toxicity in colorectal cancer patients [34].
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ABCC8 p.Cys677Thr 20638924:119:30
status: NEW122 It has been suggested that MTHFR A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma [35].
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ABCC8 p.Cys677Thr 20638924:122:54
status: NEW139 We introduced new data related to the role of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T in patients with breast cancer treated with neoadjuvant chemotherapy.
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ABCC8 p.Cys677Thr 20638924:139:58
status: NEW[hide] TYMS, MTHFR, p53 and MDR1 gene polymorphisms in br... Cancer Epidemiol. 2010 Aug;34(4):490-3. Epub 2010 Apr 3. Henriquez-Hernandez LA, Perez LF, Hernandez AG, de Leon AC, Diaz-Chico B, Rosales AM
TYMS, MTHFR, p53 and MDR1 gene polymorphisms in breast cancer patients treated with adjuvant therapy.
Cancer Epidemiol. 2010 Aug;34(4):490-3. Epub 2010 Apr 3., [PMID:20371218]
Abstract [show]
PURPOSE: The distribution of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms was investigated in 80 consecutive breast cancer patients treated with adjuvant chemotherapy. RESULTS: Observed allelic frequencies were: TSER, (2) 0.55 and (3) 0.45; MTHFR C677T, (C) 0.65 and (T) 0.35; p53 Arg72Pro, (Arg) 0.76 and (Pro) 0.24; MDR1 C3435T, (C) 0.51 and (T) 0.49. MTHFR C677T was found to be a strong predictor of the presence of multifocal tumour (odds ratio, 4.1; 95% CI, 1.1-15.7; P=0.035). CONCLUSION: Our data indicate that breast cancer patients with the C/C variant may present multifocal tumour most frequently.
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No. Sentence Comment
13 C677T is a common single nucleotide polymorphism (SNP) in exon 4 at the folate binding site of the MTHFR gene which results in alanine to valine substitution at codon 222 [10].
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ABCC8 p.Cys677Thr 20371218:13:0
status: NEW18 Several studies in vivo and Cancer Epidemiology 34 (2010) 490-493 A R T I C L E I N F O Article history: Accepted 8 March 2010 Available online 3 April 2010 Keywords: Breast cancer Adjuvant chemotherapy Multifocal tumour Polymorphism PCR-RFLP Risk factors MTHFR A B S T R A C T Purpose: The distribution of TSER (TYMS), C677T (MTHFR), Arg72Pro (p53) and C3435T (MDR1) gene polymorphisms was investigated in 80 consecutive breast cancer patients treated with adjuvant chemotherapy.
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ABCC8 p.Cys677Thr 20371218:18:320
status: NEW19 Results: Observed allelic frequencies were: TSER, (2) 0.55 and (3) 0.45; MTHFR C677T, (C) 0.65 and (T) 0.35; p53 Arg72Pro, (Arg) 0.76 and (Pro) 0.24; MDR1 C3435T, (C) 0.51 and (T) 0.49.
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ABCC8 p.Cys677Thr 20371218:19:79
status: NEW20 MTHFR C677T was found to be a strong predictor of the presence of multifocal tumour (odds ratio, 4.1; 95% CI, 1.1-15.7; P = 0.035).
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ABCC8 p.Cys677Thr 20371218:20:6
status: NEW34 Considering all these background and observations, our purpose was to investigate the distribution of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms in breast cancer patients treated with adjuvant chemotherapy.
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ABCC8 p.Cys677Thr 20371218:34:114
status: NEW48 Genotyping Polymorphic sites in TYMS (TSER), MTHFR (C677T), p53 codon 72 (Arg/Pro) and MDR1 (C3435T) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
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ABCC8 p.Cys677Thr 20371218:48:52
status: NEW53 Amplification of the DNA regions containing the polymorphic sites in TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T was made as previously reported [24].
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ABCC8 p.Cys677Thr 20371218:53:81
status: NEW72 TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T genotypic and allelic frequencies were estimated (Table 2).
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ABCC8 p.Cys677Thr 20371218:72:12
status: NEW73 Observed allelic frequencies were (%): TSER, (2) 55 and (3) 45; MTHFR C677T, (C) 65 and (T) 35; p53 Arg72Pro, (Arg) 76 and (Pro) 24; MDR1 C3435T, (C) 51 and (T) 49.
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ABCC8 p.Cys677Thr 20371218:73:70
status: NEW77 We observed a significant association between MTHFR C677T polymorphism and the presence of multifocal lesions in the tumour.
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ABCC8 p.Cys677Thr 20371218:77:52
status: NEW85 Discussion We present here for the first time a significant association between MTHFR C677T polymorphism and the presence of multifocal lesions in the tumour.
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ABCC8 p.Cys677Thr 20371218:85:86
status: NEW91 Nonetheless, we observed a significant association between MTHFR C677T polymorphism and the presence of multifocal lesions in the tumour.
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ABCC8 p.Cys677Thr 20371218:91:65
status: NEW93 C677T gene polymorphism, which decreases enzyme activity, has been associated with cancer susceptibility [27].
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ABCC8 p.Cys677Thr 20371218:93:0
status: NEW97 Finally, several studies have shown that MTHFR C677T polymorphism does not significantly contribute to the inherited genetic susceptibility to BC [27] and response to adjuvant therapy [28].
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ABCC8 p.Cys677Thr 20371218:97:47
status: NEW111 n Genotypic frequencies (n/%) Allelic frequencies (n/%) TS 28bp STR 2/2 2/3 3/3 2 3 79 26 (33) 35 (44) 18 (23) 87 (55) 71 (45) MTHFR C677T C/C C/T T/T C T 80 35 (44) 34 (42) 11 (14) 104 (65) 56 (35) p53 codon72 Arg/Arg Arg/Pro Pro/Pro Arg Pro 80 46 (58) 29 (36) 5 (6) 121 (76) 39 (24) MDR1 C3435T C/C C/T T/T C T 80 18 (23) 45 (56) 17 (21) 81 (51) 79 (49) Table 4 Logistic regression of MTHFR C677T variants and the presence of multifocal tumour in a multivariate analysis adjusted by age, BMI, menopause status, family history of BC, clinical stage, estrogen and progesterone receptor status and erbB2 expression.
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ABCC8 p.Cys677Thr 20371218:111:133
status: NEWX
ABCC8 p.Cys677Thr 20371218:111:393
status: NEW113 category) MTHFR CC 4.1 (1.1-15.7) 0.035 Table 3 Association between MTHFR C677T gene polymorphism and the presence of multifocal tumour (x2 -test).
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ABCC8 p.Cys677Thr 20371218:113:74
status: NEW117 It has been reported that the protective effect of the homozygous variant TT form of the MTHFR genotype (C677T) on the risk of colorectal cancer seems to be modified by the level of methyl diets, that is, by folate [30].
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ABCC8 p.Cys677Thr 20371218:117:105
status: NEW122 In conclusion, the distribution of TSER, MTHFR C677T, p53 Arg72Pro and MDR1 C3435T gene polymorphisms in BC patients treated with adjuvant chemotherapy was investigated.
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ABCC8 p.Cys677Thr 20371218:122:47
status: NEW123 We have shown that patients with the C/C variant of MTHFR C677T polymorphism suffer a four times higher risk of multifocal lesions in the tumour.
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ABCC8 p.Cys677Thr 20371218:123:58
status: NEW