ABCC6 p.Glu507*
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[hide] Pseudoxanthoma elasticum: genetic variations in an... Clin Chem. 2007 Oct;53(10):1734-40. Epub 2007 Aug 10. Zarbock R, Hendig D, Szliska C, Kleesiek K, Gotting C
Pseudoxanthoma elasticum: genetic variations in antioxidant genes are risk factors for early disease onset.
Clin Chem. 2007 Oct;53(10):1734-40. Epub 2007 Aug 10., [PMID:17693525]
Abstract [show]
BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder characterized by progressive calcification and fragmentation of elastic fibers in connective tissues. PXE is caused by mutations in the ABCC6 gene, which encodes the membrane transporter multidrug resistance-associated protein 6. Chronic oxidative stress was recently suggested to play a crucial role in the pathogenesis of the disease. Our aim was to investigate the association of PXE with genetic variation in genes coding for antioxidant enzymes. METHODS: We used restriction fragment length polymorphism and allele-specific PCR analyses to evaluate the distribution of single-nucleotide polymorphisms in the genes encoding catalase (CAT), superoxide dismutase 2 (SOD2), and glutathione peroxidase 1 (GPX1) in DNA samples from 117 German PXE patients and 117 healthy age- and sex-matched control individuals. RESULTS: The investigated genetic variants had previously been shown to affect the activities of these antioxidant enzymes. We found a correlation between genotype and age of disease onset for polymorphisms in CAT (c.-262C>T), SOD2 (c.47C>T), and GPX1 (c.593C>T). Furthermore, the age of disease onset was inversely correlated with the number of mutated alleles, indicating a cumulative effect on the time of disease onset [mean (SD) age of 40.9 (13.6) years, 32.4 (16.3) years, and 25.7 (15.9) years for carriers of 0, 1-2, and >2 mutated alleles, respectively; P = 0.03]. CONCLUSION: Our findings demonstrate that increased oxidative stress due to activity-affecting polymorphisms in genes encoding antioxidant enzymes leads to earlier PXE onset.
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142 b Patients who are (a) homozygous for PXE mutation p.R1141X, c.2787 ϩ 1GϾT, or c.4434delA; and (b) compound heterozygotes for 2 of the PXE mutations p.R1141X, c.2787 ϩ 1GϾT, Ex23_Ex29del, c.4182delG, p.Q378X, c.1995delG, p.E507X, and c.2835_2850del16.
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ABCC6 p.Glu507* 17693525:142:247
status: NEW