Document Detail

Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects.
MedLine Citation:
PMID:  19844255     Owner:  NLM     Status:  MEDLINE    
Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for cardiovascular disease. To identify novel genetic variants that contribute to HDL-C, we performed genome-wide scans and quantitative association studies in two study samples: a Quebec-wide study consisting of 11 multigenerational families and a study of 61 families from the Saguenay-Lac St-Jean (SLSJ) region of Quebec. The heritability of HDL-C in these study samples was 0.73 and 0.49, respectively. Variance components linkage methods identified a LOD score of 2.61 at 98 cM near the marker D16S515 in Quebec-wide families and an LOD score of 2.96 at 86 cM near the marker D16S2624 in SLSJ families. In the Quebec-wide sample, four families showed segregation over a 25.5-cM (18 Mb) region, which was further reduced to 6.6 Mb with additional markers. The coding regions of all genes within this region were sequenced. A missense variant in CHST6 segregated in four families and, with additional families, we observed a P value of 0.015 for this variant. However, an association study of this single-nucleotide polymorphism (SNP) in unrelated Quebec-wide samples was not significant. We also identified an SNP (rs11646677) in the same region, which was significantly associated with a low HDL-C (P=0.016) in the SLSJ study sample. In addition, RT-PCR results from cultured cells showed a significant difference in the expression of CHST6 and KIAA1576, another gene in the region. Our data constitute additional evidence for a locus on chromosome 16q23-24 that affects HDL-C levels in two independent French-Canadian studies.
Zari Dastani; Päivi Pajukanta; Michel Marcil; Nicholas Rudzicz; Isabelle Ruel; Swneke D Bailey; Jenny C Lee; Mathieu Lemire; Janet Faith; Jill Platko; John Rioux; Thomas J Hudson; Daniel Gaudet; James C Engert; Jacques Genest
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-21
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  18     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-18     Completed Date:  2010-05-18     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  342-7     Citation Subset:  IM    
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MeSH Terms
Cholesterol, HDL / genetics*
Chromosomes, Human, Pair 16 / genetics*
Gene Expression Regulation
Genetic Linkage*
Genetic Predisposition to Disease*
Genome, Human
Lod Score
Physical Chromosome Mapping*
RNA, Messenger / genetics,  metabolism
Sequence Analysis, DNA
Grant Support
HL 28481/HL/NHLBI NIH HHS; HL08276/HL/NHLBI NIH HHS; HL095056/HL/NHLBI NIH HHS; MOP 62834//Canadian Institutes of Health Research; P01 HL028481/HL/NHLBI NIH HHS; P01 HL028481-21A10011/HL/NHLBI NIH HHS; P01 HL028481-220011/HL/NHLBI NIH HHS; P01 HL028481-230011/HL/NHLBI NIH HHS; P01 HL028481-240011/HL/NHLBI NIH HHS; P01 HL028481-250011/HL/NHLBI NIH HHS; R01 HL082762/HL/NHLBI NIH HHS; R01 HL082762-01A1/HL/NHLBI NIH HHS; R01 HL082762-02/HL/NHLBI NIH HHS; R01 HL082762-03/HL/NHLBI NIH HHS; R01 HL082762-04/HL/NHLBI NIH HHS; R01 HL095056/HL/NHLBI NIH HHS; R01 HL095056-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Cholesterol, HDL; 0/RNA, Messenger

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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