title: Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese.
abstract: BACKGROUND
  High-density lipoprotein (HDL) is a major plasma lipoprotein directly associated with cholesterol metabolism. The ATP binding cassette transporter 1 gene (ABCA1) is one of the major genes modulating plasma levels of HDL-cholesterol (HDL-C). Rare alleles of ABCA1 associated with extreme HDL-C concentrations have not been previously investigated in the Chinese.
  
  
  METHODS
  Blood samples were collected from 470 subjects whose HDL-C concentrations were within the top 5% of the distribution, 335 subjects in the lowest 5%, and 220 within the range 5%-95%. First, we sequenced all exons of the ABCA1 gene from 50 subjects from the group with extremely high HDL-C, and 50 from the group with extremely low HDL-C concentrations. Next, in the remaining subjects, we genotyped the non-synonymous variants identified exclusively with either extreme group.
  
  
  RESULTS
  Four novel non-synonymous alleles were identified; all were rare. Alleles c.3029C>T (p.Ala1010Val) and c.5399A>G (p.Asn1800Ser) were found exclusively in the low group, c.2031C>A (p.Asp677Glu) and c.2660G>T (p.Cys887Phe) exclusively in the high group.
  
  
  CONCLUSIONS
  Our results show that some rare alleles of ABCA1 are associated with marked phenotypes, supporting the "rare-variant common-disease" hypothesis. Certain alleles also provide tools for identifying individuals at high risk of dyslipidaemia, allowing for early therapeutic intervention.
authors.affiliation: Department of Medical Genetics, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Suwei
authors.initials: S
authors.lastname: Hu
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Hao
authors.forename: Minqi
authors.initials: M
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Weijiao
authors.initials: W
authors.lastname: Liao
authors.forename: Desheng
authors.initials: D
authors.lastname: Wan
authors.forename: Haiyun
authors.initials: H
authors.lastname: Wei
authors.forename: Yueting
authors.initials: Y
authors.lastname: Gao
authors.forename: Jinglan
authors.initials: J
authors.lastname: Shan
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Maj
authors.initials: M
authors.lastname: Hultén
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002681:China / Q000208:ethnology; D008076:Cholesterol, HDL / Q000378:metabolism*; D017124:Conserved Sequence; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D051381:Rats; D013045:Species Specificity; D019914:Taq Polymerase / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D019914:Taq Polymerase