Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.
BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of...
| Hoofdauteurs: | , , , , , , , , , , , , , , |
|---|---|
| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2010
|
| _version_ | 1826288745854271488 |
|---|---|
| author | Sarwar, N Sandhu, MS Ricketts, S Butterworth, A Di Angelantonio, E Boekholdt, S Ouwehand, W Watkins, H Samani, N Saleheen, D Lawlor, D Reilly, M Hingorani, A Talmud, P Danesh, J |
| author_facet | Sarwar, N Sandhu, MS Ricketts, S Butterworth, A Di Angelantonio, E Boekholdt, S Ouwehand, W Watkins, H Samani, N Saleheen, D Lawlor, D Reilly, M Hingorani, A Talmud, P Danesh, J |
| author_sort | Sarwar, N |
| collection | OXFORD |
| description | BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. FUNDING: British Heart Foundation, UK Medical Research Council, Novartis. |
| first_indexed | 2024-03-07T02:18:21Z |
| format | Journal article |
| id | oxford-uuid:a30ba46f-3282-4b9c-84ac-e494b4ccadb7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:18:21Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:a30ba46f-3282-4b9c-84ac-e494b4ccadb72022-03-27T02:24:06ZTriglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a30ba46f-3282-4b9c-84ac-e494b4ccadb7EnglishSymplectic Elements at Oxford2010Sarwar, NSandhu, MSRicketts, SButterworth, ADi Angelantonio, EBoekholdt, SOuwehand, WWatkins, HSamani, NSaleheen, DLawlor, DReilly, MHingorani, ATalmud, PDanesh, JBACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. FUNDING: British Heart Foundation, UK Medical Research Council, Novartis. |
| spellingShingle | Sarwar, N Sandhu, MS Ricketts, S Butterworth, A Di Angelantonio, E Boekholdt, S Ouwehand, W Watkins, H Samani, N Saleheen, D Lawlor, D Reilly, M Hingorani, A Talmud, P Danesh, J Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. |
| title | Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. |
| title_full | Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. |
| title_fullStr | Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. |
| title_full_unstemmed | Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. |
| title_short | Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. |
| title_sort | triglyceride mediated pathways and coronary disease collaborative analysis of 101 studies |
| work_keys_str_mv | AT sarwarn triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT sandhums triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT rickettss triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT butterwortha triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT diangelantonioe triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT boekholdts triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT ouwehandw triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT watkinsh triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT samanin triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT saleheend triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT lawlord triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT reillym triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT hingorania triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT talmudp triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies AT daneshj triglyceridemediatedpathwaysandcoronarydiseasecollaborativeanalysisof101studies |