title: Phenotype-genotype analyses of clinically diagnosed Malaysian familial hypercholestrolemic patients.
abstract: BACKGROUND
  Familial hypercholesterolemia and familial defective apo lipoprotein B are genetic disorders caused by defects in the low-density lipoprotein receptor gene and apo lipoprotein B 100 genes, respectively. The clinical phenotype of both diseases is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature coronary heart disease.
  
  
  OBJECTIVE
  The aim of this study is to perform an association study between different gene sequence variants in low-density lipoprotein and apo lipoprotein B 100 genes to the clinical finding and lipid profile parameters of the study subjects.
  
  
  METHODS
  A group of 164 familial hypercholesterolemic patients were recruited. The promoter region, exon 2-15 of the low density lipoprotein gene and parts of exon 26 and 29 of apo lipoprotein B 100 gene were screened by Denaturating Gradient High Performance Liquid Chromatography.
  
  
  RESULTS
  For the apo lipoprotein B 100 gene, those with apo lipoprotein B 100 gene mutation have a significantly higher frequency of cardiovascular disease (P = 0.045), higher low density lipoprotein cholesterol and total cholesterol: high density lipoprotein cholesterol ratio than those without mutation (P = 0.03 and 0.02, respectively). For the low density lipoprotein gene defect those with frame shift mutation group showed the worst clinical presentation in terms of low density lipoprotein cholesterol level and cardiovascular frequency.
  
  
  CONCLUSIONS
  There was a statistically significant association between mutations of low density lipoprotein gene and apo lipoprotein B 100 genes and history of cardiovascular disease, younger age of presentation, family history of hyperlipidemia, tendon xanthoma and low density lipoprotein cholesterol level.
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia. alyaa_1974@yahoo.com
authors.forename: Alyaa
authors.initials: A
authors.lastname: Al-Khateeb
authors.forename: Hassanain
authors.initials: H
authors.lastname: Al-Talib
authors.forename: Mohd S
authors.initials: MS
authors.lastname: Mohamed
authors.forename: Zurkurnai
authors.initials: Z
authors.lastname: Yusof
authors.forename: Bin A
authors.initials: BA
authors.lastname: Zilfalil
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D053299:Apolipoprotein B-100; D008055:Lipids; D011973:Receptors, LDL