Dataset Information

S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies.

ABSTRACT:

Background

Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies.

Methods

The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively.

Results

S447X carriers tended to have lower TG and higher HDL-C concentrations than noncarriers. The S447X variant was associated with a lower risk of CHD in the NHS; the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies.

Conclusions

The LPL S447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all 3 cohorts. Lipoprotein lipase is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.

SUBMITTER: Jensen MK

PROVIDER: S-EPMC3183417 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Publications

S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies.

Jensen Majken K MK Rimm Eric B EB Rader Daniel D Schmidt Erik B EB Sørensen Thorkild I A TI Vogel Ulla U Overvad Kim K Mukamal Kenneth J KJ

American heart journal 20090201 2

<h4>Background</h4>Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies.<h4>Methods</h4>The S447X var ...[more]

PMID: 19185650

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Project description:BackgroundRemnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.Methods and resultsWe analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.ConclusionRLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.Clinical trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

Project description:BackgroundDepression, as an independent risk factor, can lead to a substantially increased risk of coronary heart disease (CHD). The overall body of evidence involving depression and CHD is not consistent. Therefore, we performed an update meta-analysis to evaluate the association between depression and the risk of patients with CHD.MethodsStudies were identified through a comprehensive literature search of the PubMed, Embase, and the Cochrane Library database from its inception to 28 September 2021 for titles/abstracts with restricted to English language articles. The literature was screened according to the inclusion and exclusion criteria. Along with data extraction, we evaluated the quality of eligible studies using the Newcastle-Ottawa Scale (NOS). The primary outcome was fatal or non-fatal CHD. We calculated relative risk (RR) with 95% confidence intervals (CIs) using a random-effects models. The protocol was registered in the PROSPERO registration (registration number CRD42021271259).ResultsFrom 9,151 records, we included 26 prospective cohort studies published from 1998 to 2018, consisting of 402,597 patients. Either in depression-exposured group or non-depression-exposured group, the mean age of all participants ranged from 18 to 99 years. Moreover, the NOS scores of these studies are eventually indicated that the quality of these eligible studies was reliable. In general, the pooled results showed that patients with depression had a higher risk of CHD compared to patients without depression (RR = 1.21, 95% CI: 1.14-1.29). Additionally, the funnel plot appeared to be asymmetry, indicating there existing publication bias for the pooled results between depression and CHD. A sensitivity analysis was used to assess the stability of the relationship between depression and CHD that indicating the results robust (RR = 1.15, 95% CI: 1.09-1.21).ConclusionDepression may increase risk of CHD. Future studies on the share pathogenic mechanisms of both depression and CHD may develop novel therapies.

Dataset Information

S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies.

Background

Methods

Results

Conclusions

Publications

S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies.

Similar Datasets

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