select ad.sno,ad.journal,ad.title,ad.author_names,ad.abstract,ad.abstractlink,j.j_name,vi.* from articles_data ad left join journals j on j.journal=ad.journal left join vol_issues vi on vi.issue_id_en=ad.issue_id where ad.sno_en='47769' and ad.lang_id='5' and j.lang_id='5' and vi.lang_id='5' Common Variants in 6 Lipid-Related Genes Discovered by High- | 47769
Cardiologie clinique et expérimentale

Cardiologie clinique et expérimentale
Libre accès

ISSN: 2155-9880

Abstrait

Common Variants in 6 Lipid-Related Genes Discovered by High-Resolution DNA Melting Analysis and Their Association with Plasma Lipids

John F. Carlquist, Jason T. McKinney, Benjamin D. Horne, Nicola J. Camp, Lisa Cannon-Albright, Joseph B. Muhlestein, Paul Hopkins, Jessica L. Clarke, Chrissa P. Mower, James J. Park, Zachary P. Nicholas, John A. Huntinghouse and Jeffrey L. Anderson

Background: Total cholesterol was among the earliest identified risk factors for coronary heart disease (CHD). We sought to identify genetic variants in six genes associated with lipid metabolism and estimate their respective contribution to risk for CHD.

Methods: For 6 lipid-associated genes ( LCAT, CETP , LIPC , LPL , SCARB1 , and ApoF ) we scanned exons, 5’ and 3’ untranslated regions, and donor and acceptor splice sites for variants using Hi-Res Melting® curve analysis (HRMCA) with confirmation by cycle sequencing. Healthy subjects were used for SNP discovery (n=64), haplotype determination/tagging SNP discovery (n=339), and lipid association testing (n=786).

Results: In 17,840 bases of interrogated sequence, 90 variant SNPs were identified; 19 (21.1%) previously unreported. Thirty-four variants (37.8%) were exonic(16 non-synonymous), 28 (31.1%) in intron-exon boundaries, and 28 (31.1%) in the 5’ and 3’ untranslated regions. Compared to cycle sequencing, HRMCA had sensitivity of 99.4% and specificity of 97.7%. Tagging SNPs (n=38) explained >90% of the variation in the 6 genes and identified linkage disequilibrium (LD) groups. Significant beneficial lipid profiles were observed for CETP LD group 2, LIPC LD groups 1 and 7, and SCARB1 LD groups 1, 3 and 4. Risk profiles worsened for CETP LD group 3, LPL LD group 4.

Conclusions: These findings demonstrate the feasibility, sensitivity, and specificity of HRMCA for SNP discovery. Variants identified in these genes may be used to predict lipid-associated risk and reclassification of clinical CHD risk.

Clause de non-responsabilité: Ce résumé a été traduit à l'aide d'outils d'intelligence artificielle et n'a pas encore été révisé ou vérifié.
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