Large-scale candidate gene analysis of HDL particle features.
BACKGROUND: HDL cholesterol (HDL-C) is an established marker of cardiovascular risk with significant genetic determination. However, HDL particles are not homogenous, and refined HDL phenotyping may improve insight into regulation of HDL metabolism. We therefore assessed HDL particles by NMR spectro...
| المؤلفون الرئيسيون: | , , , , , , , , , , , , , , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
Public Library of Science
2011
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| _version_ | 1826301110984376320 |
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| author | Kaess, B Tomaszewski, M Braund, P Stark, K Rafelt, S Fischer, M Hardwick, R Nelson, C Debiec, R Huber, F Kremer, W Kalbitzer, H Rose, L Chasman, D Hopewell, J Clarke, R Burton, P Tobin, MD Hengstenberg, C Samani, N |
| author_facet | Kaess, B Tomaszewski, M Braund, P Stark, K Rafelt, S Fischer, M Hardwick, R Nelson, C Debiec, R Huber, F Kremer, W Kalbitzer, H Rose, L Chasman, D Hopewell, J Clarke, R Burton, P Tobin, MD Hengstenberg, C Samani, N |
| author_sort | Kaess, B |
| collection | OXFORD |
| description | BACKGROUND: HDL cholesterol (HDL-C) is an established marker of cardiovascular risk with significant genetic determination. However, HDL particles are not homogenous, and refined HDL phenotyping may improve insight into regulation of HDL metabolism. We therefore assessed HDL particles by NMR spectroscopy and conducted a large-scale candidate gene association analysis. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma HDL-C and determined mean HDL particle size and particle number by NMR spectroscopy in 2024 individuals from 512 British Caucasian families. Genotypes were 49,094 SNPs in >2,100 cardiometabolic candidate genes/loci as represented on the HumanCVD BeadChip version 2. False discovery rates (FDR) were calculated to account for multiple testing. Analyses on classical HDL-C revealed significant associations (FDR<0.05) only for CETP (cholesteryl ester transfer protein; lead SNP rs3764261: p = 5.6*10(-15)) and SGCD (sarcoglycan delta; rs6877118: p = 8.6*10(-6)). In contrast, analysis with HDL mean particle size yielded additional associations in LIPC (hepatic lipase; rs261332: p = 6.1*10(-9)), PLTP (phospholipid transfer protein, rs4810479: p = 1.7*10(-8)) and FBLN5 (fibulin-5; rs2246416: p = 6.2*10(-6)). The associations of SGCD and Fibulin-5 with HDL particle size could not be replicated in PROCARDIS (n = 3,078) and/or the Women's Genome Health Study (n = 23,170). CONCLUSIONS: We show that refined HDL phenotyping by NMR spectroscopy can detect known genes of HDL metabolism better than analyses on HDL-C. |
| first_indexed | 2024-03-07T05:27:25Z |
| format | Journal article |
| id | oxford-uuid:e10c9876-bb91-4ba0-933e-cf409288ff2d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:27:25Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:e10c9876-bb91-4ba0-933e-cf409288ff2d2022-03-27T09:51:52ZLarge-scale candidate gene analysis of HDL particle features.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e10c9876-bb91-4ba0-933e-cf409288ff2dEnglishSymplectic Elements at OxfordPublic Library of Science2011Kaess, BTomaszewski, MBraund, PStark, KRafelt, SFischer, MHardwick, RNelson, CDebiec, RHuber, FKremer, WKalbitzer, HRose, LChasman, DHopewell, JClarke, RBurton, PTobin, MDHengstenberg, CSamani, NBACKGROUND: HDL cholesterol (HDL-C) is an established marker of cardiovascular risk with significant genetic determination. However, HDL particles are not homogenous, and refined HDL phenotyping may improve insight into regulation of HDL metabolism. We therefore assessed HDL particles by NMR spectroscopy and conducted a large-scale candidate gene association analysis. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma HDL-C and determined mean HDL particle size and particle number by NMR spectroscopy in 2024 individuals from 512 British Caucasian families. Genotypes were 49,094 SNPs in >2,100 cardiometabolic candidate genes/loci as represented on the HumanCVD BeadChip version 2. False discovery rates (FDR) were calculated to account for multiple testing. Analyses on classical HDL-C revealed significant associations (FDR<0.05) only for CETP (cholesteryl ester transfer protein; lead SNP rs3764261: p = 5.6*10(-15)) and SGCD (sarcoglycan delta; rs6877118: p = 8.6*10(-6)). In contrast, analysis with HDL mean particle size yielded additional associations in LIPC (hepatic lipase; rs261332: p = 6.1*10(-9)), PLTP (phospholipid transfer protein, rs4810479: p = 1.7*10(-8)) and FBLN5 (fibulin-5; rs2246416: p = 6.2*10(-6)). The associations of SGCD and Fibulin-5 with HDL particle size could not be replicated in PROCARDIS (n = 3,078) and/or the Women's Genome Health Study (n = 23,170). CONCLUSIONS: We show that refined HDL phenotyping by NMR spectroscopy can detect known genes of HDL metabolism better than analyses on HDL-C. |
| spellingShingle | Kaess, B Tomaszewski, M Braund, P Stark, K Rafelt, S Fischer, M Hardwick, R Nelson, C Debiec, R Huber, F Kremer, W Kalbitzer, H Rose, L Chasman, D Hopewell, J Clarke, R Burton, P Tobin, MD Hengstenberg, C Samani, N Large-scale candidate gene analysis of HDL particle features. |
| title | Large-scale candidate gene analysis of HDL particle features. |
| title_full | Large-scale candidate gene analysis of HDL particle features. |
| title_fullStr | Large-scale candidate gene analysis of HDL particle features. |
| title_full_unstemmed | Large-scale candidate gene analysis of HDL particle features. |
| title_short | Large-scale candidate gene analysis of HDL particle features. |
| title_sort | large scale candidate gene analysis of hdl particle features |
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