Linked Life Data

9536518

Source:http://linkedlifedata.com/resource/pubmed/id/9536518

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-6-1
pubmed:abstractText
The correlation of polymorphic DNA haplotype of the alpha-L-iduronidase (IDUA) gene and IDUA activity in Chinese subjects was investigated. Genomic DNA extracted from 85 randomly sampled normal individuals was used to amplify fragments containing the polymorphic change site A8, Q33H (exon 1), R105Q (exon 3), A361T (exon 8), or V454I (exon 9). The PCR amplified products were analyzed by means of restriction fragment length polymorphism (RFLP) or allele specific oligonucleotide (ASO) hybridization. Leukocytes were isolated from the above 85 samples, and their IDUA activities were determined. A wide range of IDUA activity (50-300 nmol/h/mg cell protein) with an average of 156 nmol/h/mg cell protein was observed. When the allele frequency was compared between individuals with IDUA activity below 90% or above 110% of the average, a bias toward the common allele "1" of Q33H (Gln33) was detected in individuals with higher IDUA activity. Conversely, the polymorphic allele "2" of R105Q (Gln105), A361T (Thr361), and V454I (Ile454) was found in the higher IDUA activity group. Linkage disequilibrium analysis of the haplotype data revealed strong nonrandom association among the polymorphic alleles of R105Q, A361T, and V454I. Of the haplotypes constructed by Q33H, R105Q, A361T, and V454I, a positive correlation between haplotype 1,2,2,2 (Gln33, Gln105, Thr361, Ile454) and IDUA activity was observed. The IDUA activity was found to increase with Gln105, Thr361, or Ile454 polymorphic changes by mutagenesis and expression of IDUA cDNA in COS-7 cells. By combining the positive effect of Gln105, Thr361, and Ile454 in one cDNA construct, it may be possible to produce a high activity IDUA protein for MPS I enzyme replacement therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0255-6596
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31-8
pubmed:dateRevised
2008-2-26
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Human alpha-L-iduronidase (IDUA) gene: correlation of polymorphic DNA haplotype and IDUA activity in Chinese population.
pubmed:affiliation
Department of Biology, National Taiwan Normal University, Taipei, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't