Haplotype analysis and possible founder effect at the R778L mutation of the ATP7B gene in Korean patients with Wilson's disease / 대한간학회지
The Korean Journal of Hepatology
;
: 309-319, 2009.
Article
in Korean
| WPRIM
| ID: wpr-181187
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Haplotypes
/
Adenosine Triphosphatases
/
Founder Effect
/
Microsatellite Repeats
/
Amino Acid Substitution
/
Cation Transport Proteins
/
Republic of Korea
/
Gene Frequency
/
Genotype
/
Hepatolenticular Degeneration
Type of study:
Prognostic study
Limits:
Humans
Country/Region as subject:
Asia
Language:
Korean
Journal:
The Korean Journal of Hepatology
Year:
2009
Type:
Article
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