Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis
<p>Abstract</p> <p>Background</p> <p>Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-10-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/10/111 |
| _version_ | 1819280577971355648 |
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| author | Gotto Antonio M Willerson James T Lombardi Raffaella Todd Josh Cilingiroglu Mehmet Chen Suet Ballantyne Christie M Marian AJ |
| author_facet | Gotto Antonio M Willerson James T Lombardi Raffaella Todd Josh Cilingiroglu Mehmet Chen Suet Ballantyne Christie M Marian AJ |
| author_sort | Gotto Antonio M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis.</p> <p>Methods</p> <p>We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR).</p> <p>Results</p> <p>Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in <it>APOA5, APOC2</it>, <it>CETP, LPL </it>and <it>LIPC </it>(each q ≤0.01). Likewise, plasma apo A-I levels, available in the LCAS subset, were associated with SNPs in <it>CETP</it>, <it>APOA5</it>, and <it>APOC2 </it>as well as with BMI, sex and age (all q values ≤0.03). The <it>APOA5 </it>variant S19W was also associated with minimal lumen diameter (MLD) of coronary atherosclerotic lesions, a quantitative index of severity of coronary atherosclerosis (q = 0.018); mean number of coronary artery occlusions (p = 0.034) at the baseline and progression of coronary atherosclerosis, as indicated by the loss of MLD.</p> <p>Conclusion</p> <p>Putatively functional variants of <it>APOA2</it>, <it>APOA5, APOC2</it>, <it>CETP, LPL</it>, <it>LIPC </it>and <it>SOAT2 </it>are independent genetic determinants of plasma HDL-C levels. The non-synonymous S19W SNP in <it>APOA5 </it>is also an independent determinant of plasma apo A-I level, severity of coronary atherosclerosis and its progression.</p> |
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| format | Article |
| id | doaj.art-e4c28fd4e5fb4759b3713d873d668603 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-24T00:46:01Z |
| publishDate | 2009-10-01 |
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| series | BMC Medical Genetics |
| spelling | doaj.art-e4c28fd4e5fb4759b3713d873d6686032022-12-21T17:23:48ZengBMCBMC Medical Genetics1471-23502009-10-0110111110.1186/1471-2350-10-111Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosisGotto Antonio MWillerson James TLombardi RaffaellaTodd JoshCilingiroglu MehmetChen SuetBallantyne Christie MMarian AJ<p>Abstract</p> <p>Background</p> <p>Plasma level of high-density lipoprotein-cholesterol (HDL-C), a heritable trait, is an important determinant of susceptibility to atherosclerosis. Non-synonymous and regulatory single nucleotide polymorphisms (SNPs) in genes implicated in HDL-C synthesis and metabolism are likely to influence plasma HDL-C, apolipoprotein A-I (apo A-I) levels and severity of coronary atherosclerosis.</p> <p>Methods</p> <p>We genotyped 784 unrelated Caucasian individuals from two sets of populations (Lipoprotein and Coronary Atherosclerosis Study- LCAS, N = 333 and TexGen, N = 451) for 94 SNPs in 42 candidate genes by 5' nuclease assays. We tested the distribution of the phenotypes by the Shapiro-Wilk normality test. We used Box-Cox regression to analyze associations of the non-normally distributed phenotypes (plasma HDL-C and apo A-I levels) with the genotypes. We included sex, age, body mass index (BMI), diabetes mellitus (DM), and cigarette smoking as covariates. We calculated the q values as indicators of the false positive discovery rate (FDR).</p> <p>Results</p> <p>Plasma HDL-C levels were associated with sex (higher in females), BMI (inversely), smoking (lower in smokers), DM (lower in those with DM) and SNPs in <it>APOA5, APOC2</it>, <it>CETP, LPL </it>and <it>LIPC </it>(each q ≤0.01). Likewise, plasma apo A-I levels, available in the LCAS subset, were associated with SNPs in <it>CETP</it>, <it>APOA5</it>, and <it>APOC2 </it>as well as with BMI, sex and age (all q values ≤0.03). The <it>APOA5 </it>variant S19W was also associated with minimal lumen diameter (MLD) of coronary atherosclerotic lesions, a quantitative index of severity of coronary atherosclerosis (q = 0.018); mean number of coronary artery occlusions (p = 0.034) at the baseline and progression of coronary atherosclerosis, as indicated by the loss of MLD.</p> <p>Conclusion</p> <p>Putatively functional variants of <it>APOA2</it>, <it>APOA5, APOC2</it>, <it>CETP, LPL</it>, <it>LIPC </it>and <it>SOAT2 </it>are independent genetic determinants of plasma HDL-C levels. The non-synonymous S19W SNP in <it>APOA5 </it>is also an independent determinant of plasma apo A-I level, severity of coronary atherosclerosis and its progression.</p>http://www.biomedcentral.com/1471-2350/10/111 |
| spellingShingle | Gotto Antonio M Willerson James T Lombardi Raffaella Todd Josh Cilingiroglu Mehmet Chen Suet Ballantyne Christie M Marian AJ Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis BMC Medical Genetics |
| title | Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis |
| title_full | Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis |
| title_fullStr | Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis |
| title_full_unstemmed | Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis |
| title_short | Candidate genetic analysis of plasma high-density lipoprotein-cholesterol and severity of coronary atherosclerosis |
| title_sort | candidate genetic analysis of plasma high density lipoprotein cholesterol and severity of coronary atherosclerosis |
| url | http://www.biomedcentral.com/1471-2350/10/111 |
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