Korean J Hepatol.
2009 Sep;15(3):309-319. 10.3350/kjhep.2009.15.3.309.
Haplotype analysis and possible founder effect at the R778L mutation of the ATP7B gene in Korean patients with Wilson's disease
- Affiliations
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- 1Division of Pediatric Gastroenterology, Hepatology and Nutrition, School of Medicine, Seoul National University, Korea. jkseo@plaza.snu.ac.kr
- 2Department of Laboratory Medicine, Samsung Medical center, Sung Kyun Kwan University, Seoul, Korea.
- KMID: 1374959
- DOI: http://doi.org/10.3350/kjhep.2009.15.3.309
Abstract
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BACKGROUND/AIMS: Wilson's disease (WD) is an inherited disorder of copper metabolism caused by alteration of the P-type adenosine triphosphatase (ATP) 7B gene. In this study, we analyzed the frequency of well-known mutations and constructed the first haplotypes for Koreans. In addition, we evaluated whether a founder effect existed in Korean patients with WD.
METHODS
We obtained DNA samples from 21 patients with WD and their parents (total cohort n=63). ATP7B gene mutations were identified by direct sequencing methods, and microsatellite typing was performed at D13S315, D13S1325, and D13S316 with fluorescent dye-labeled primers. Any founder effect was identified by using 42 normal alleles from parents with a normal phenotype as a control group. The chi-square test and Fisher's exact test were used for statistical analysis.
RESULTS
Three common mutations were found in 23 chromosomes obtained from 21 patients: the R778L mutation at exon 8 (15/23, 65.2%), the A874V mutation at exon 11 (6/23, 26.1%), and the N1270S mutation at exon 18 (2/23, 8.7%). D13S315 and D13S316 showed linkage disequilibrium at alleles 5 and 4, respectively, in patients with the R778L mutation (P=0.0157 and 0.0001, respectively). The haplotype made up of these two alleles occurred significantly more frequently in patients with the R778L mutation (5-R778L-4, D13S315-mutation-D13S316) than in the controls (P=0.0018).
CONCLUSIONS
The arche haplotype of the ATP7B gene in Korean patients with WD may be 5-R778L-4 (D13S315.mutation.D13S316), and it might illustrate a founder effect.
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