Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese
Hu, Suwei, Zhong, Yanfang, Hao, Yuantao, Luo, Minqi, Zhou, Yan, Guo, Hui, Liao, Weijiao, Wan, Desheng, Wei, Haiyun, Gao, Yueting, Shan, Jinglan, Hu, Bin, Hultén, Maj A. and Wang, Yiming. (2009) Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese. Clinical Chemistry and Laboratory Medicine, Vol.47 (No.10). pp. 1239-1245. ISSN 1434-6621Full text not available from this repository.
Official URL: http://dx.doi.org/10.1515/CCLM.2009.284
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. Clin Chem Lab Med 2009;47:1239-45.
|Item Type:||Journal Article|
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Journal or Publication Title:||Clinical Chemistry and Laboratory Medicine|
|Publisher:||Walter de Gruyter GmbH & Co. KG|
|Number of Pages:||7|
|Page Range:||pp. 1239-1245|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||985 Project of China, Natural Science Foundation of Guangdong Province, Guangzhou Municipal Science and Technology Foundation|
|Grant number:||031673, 2002Z3-C7191, 2004Z3-C7501|
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