TY - JOUR
T1 - Mutation in the PCSK9 gene in Omani Arab subjects with autosomal dominant hypercholesterolemia and its efect on PCSK9 protein structure
AU - Al-Waili, Khalid
AU - Al-Zidi, Ward Al Muna
AU - Al-Abri, Abdul Rahim
AU - Al-Rasadi, Khalid
AU - Al-Sabti, Hilal Ali
AU - Shah, Karna
AU - Al-Futaisi, Abdullah
AU - Al-Zakwani, Ibrahim
AU - Banerjee, Yajnavalka
PY - 2013
Y1 - 2013
N2 - Proprotein convertase subtilisin/kexin type (PCSK9) is a crucial protein in LDL cholesterol (LDL-C) metabolism by virtue of its pivotal role in the degradation of the LDL receptor. Mutations in the PCSK9 gene have previously been found to segregate with autosomal dominant familial hypercholesterolemia (ADFH). In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed for two patients with a clinical diagnosis of familial hypercholesterolemia where mutation in the LDL-receptor gene hasn't been excluded. One missense mutation was detected in the exon 9 PCSK9 gene in the two ADFH patients. Te patients were found to be heterozygote for Ile474Val (SNP rs562556). Using an array of in silico tools, we have investigated the efect of the above mutation on diferent structural levels of the PCSK9 protein. Although, the mutation has already been reported in the literature for other populations, to the best of our knowledge this is the frst report of a mutation in the PCSK9 gene from the Arab population, including the Omani population.
AB - Proprotein convertase subtilisin/kexin type (PCSK9) is a crucial protein in LDL cholesterol (LDL-C) metabolism by virtue of its pivotal role in the degradation of the LDL receptor. Mutations in the PCSK9 gene have previously been found to segregate with autosomal dominant familial hypercholesterolemia (ADFH). In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed for two patients with a clinical diagnosis of familial hypercholesterolemia where mutation in the LDL-receptor gene hasn't been excluded. One missense mutation was detected in the exon 9 PCSK9 gene in the two ADFH patients. Te patients were found to be heterozygote for Ile474Val (SNP rs562556). Using an array of in silico tools, we have investigated the efect of the above mutation on diferent structural levels of the PCSK9 protein. Although, the mutation has already been reported in the literature for other populations, to the best of our knowledge this is the frst report of a mutation in the PCSK9 gene from the Arab population, including the Omani population.
KW - Autosomal dominant hypercholesterolemia
KW - Mutation
KW - PCSK9 protien
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U2 - 10.5001/omj.2013.11
DO - 10.5001/omj.2013.11
M3 - Article
C2 - 23386946
AN - SCOPUS:84873302752
SN - 1999-768X
VL - 28
SP - 48
EP - 52
JO - Oman Medical Journal
JF - Oman Medical Journal
IS - 1
ER -