title: Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease.
abstract: BACKGROUND
  The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history.
  
  
  RESULTS
  Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h2 48% - 70%; P < 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multi-point analysis (LOD score 7.42, P < 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (P < 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (P < 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (P < 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis.
  
  
  CONCLUSIONS
  The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians.
authors.affiliation: Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bangalore, India. jayashreeshanker@triindia.org.in
authors.forename: Jayashree
authors.initials: J
authors.lastname: Shanker
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Perumal
authors.forename: Veena S
authors.initials: VS
authors.lastname: Rao
authors.forename: Natesha B
authors.initials: NB
authors.lastname: Khadrinarasimhiah
authors.forename: Shibu
authors.initials: S
authors.lastname: John
authors.forename: Sridhara
authors.initials: S
authors.lastname: Hebbagodi
authors.forename: Manjari
authors.initials: M
authors.lastname: Mukherjee
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Kakkar
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics*; D001208:Asia / Q000208:ethnology; D044466:Asian People / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007194:India; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D012044:Regression Analysis
chemical_list: C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D005819:Genetic Markers
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