title: Associations of polymorphisms in the apolipoprotein A1/C3/A4/A5 gene cluster with familial combined hyperlipidaemia in Hong Kong Chinese.
abstract: BACKGROUND
  Familial combined hyperlipidaemia (FCH) is the most common genetic dyslipidaemia associated with coronary artery disease. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A4/A5 gene cluster are associated with FCH in Caucasians and with elevated triglycerides (TG) in various ethnic groups. We examined these associations with FCH in Hong Kong Chinese.
  
  
  METHODS
  Fifty-six Chinese FCH patients and 176 unrelated controls were studied. Thirteen SNPs in the APOA1/C3/A4/A5 cluster were genotyped.
  
  
  RESULTS
  Four alleles in APOA5 were associated with FCH (P<0.001). The -1131T>C (rs662799) and -3A>G (rs651821) SNPs in APOA5 were in almost complete linkage disequilibrium (LD, r(2)=0.99), and their minor alleles were more frequent (P<0.001) in FCH than controls (0.60 vs. 0.24). The odds ratio (OR) for FCH was 6.2 (95% CI, 2.6-14.8) and 6.1 (2.6-14.6) per copy of -1131C and -3G, respectively, and 24.6 (8.4-72.0) and 24.4 (8.4-70.9) in -1131C and -3G homozygotes, respectively, as compared to wild-type homozygotes. The 1891T>C (rs2266788) SNP was in LD (r(2)=0.68) with -1131T>C and -3A>G, and the minor allele was more frequent in FCH than controls (0.42 vs. 0.19, P<0.001). The 553G>T (rs2075291) nonsynonymous variant was also associated with FCH (0.15 vs. 0.04, P=0.001) and, along with -3A>G (or -1131T>C) and 1891T>C, contributed to haplotypes predicting FCH. The two tightly linked SNPs, -1131T>C and -3A>G polymorphism were significantly associated with lipid traits in all subjects combined, with variant homozygous subjects having higher TG and LDL-C and lower HDL-C levels.
  
  
  CONCLUSIONS
  Some common polymorphisms and haplotypes in APOA5 are closely associated with FCH in Hong Kong Chinese, and these differ from those found in Caucasians.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
authors.forename: Zhi-Kai
authors.initials: ZK
authors.lastname: Liu
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics*; D044466:Asian People; D002681:China; D005260:Female; D006239:Haplotypes; D006723:Hong Kong; D006801:Humans; D006949:Hyperlipidemias / Q000208:ethnology* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: C505693:APOA1 protein, human; C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; C022205:apolipoprotein A-IV