Document Detail

Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes.
MedLine Citation:
PMID:  21900290     Owner:  NLM     Status:  MEDLINE    
AIMS: To examine the relations between genetic loci, plasma lipoprotein(a) [Lp(a)] levels, and cardiovascular disease (CVD) risk among diabetic patients and compare with the observations in the general population.
METHODS AND RESULTS: In two prospective cohorts of patients with type 2 diabetes (n= 2308) from the Nurses' Health Study and the Health Professional Follow-Up Study, we performed (i) genome-wide association (GWA) scans for plasma Lp(a); (ii) prospective analysis of plasma Lp(a) for CVD risk and mortality; and (iii) genetic association analysis for CVD risk and mortality. Meta-analysis of the two GWA scans yielded 71 single-nucleotide polymorphisms (SNPs) on chromosome 6q associated with plasma Lp(a) levels at a genome-wide significance level (P< 5 × 10(-8)). The SNP rs10455872 in LPA was most strongly associated with Lp(a) (P= 4.60 × 10(-39)). Forward-selection analysis indicated that rs10455872 and other five SNPs in a region encompassing LPA, PLG, SLC22A3, and LPAL2 genes were independently associated with Lp(a) levels and jointly explained ∼20% of variation in diabetic patients. In prospective analysis, we did not find any significant association between plasma levels and CVD incidence; the relative risk for coronary heart disease (CHD), CVD, and CVD death was 1.05 [95% confidence interval (CI): 0.95-1.15], 1.05 (0.96-1.15), and 1.21 (0.99-1.47) per 1-SD higher log-transformed Lp(a) levels, respectively. Consistently, none of the Lp(a) SNPs were associated with CVD risk or mortality (all P> 0.09). For the best SNP rs10455872 for plasma Lp(a) levels, the OR for CHD, CVD, and CVD death was 0.94 (95% CI: 0.69-1.28), 0.97 (0.72-1.29), and 1.23 (0.79-1.92), respectively. The genetic effect on CHD risk showed a significant heterogeneity between the diabetic and the general populations (P= 0.006).
CONCLUSION: Our data indicate that the effect of Lp(a) on CVD risk among diabetic patients might be different from that in the general population. Diabetes status may attenuate the relation between Lp(a) and cardiovascular risk.
Qibin Qi; Tsegaselassie Workalemahu; Cuilin Zhang; Frank B Hu; Lu Qi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2011-09-06
Journal Detail:
Title:  European heart journal     Volume:  33     ISSN:  1522-9645     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-02     Completed Date:  2012-03-29     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  England    
Other Details:
Languages:  eng     Pagination:  325-34     Citation Subset:  IM    
Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA.
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MeSH Terms
Coronary Disease / blood,  genetics,  mortality
Diabetes Mellitus, Type 2 / blood,  genetics*,  mortality
Diabetic Angiopathies / blood,  genetics*,  mortality
Genome-Wide Association Study
Lipoprotein(a) / genetics*,  metabolism
Middle Aged
Myocardial Infarction / blood,  genetics,  mortality
Polymorphism, Single Nucleotide / genetics*
Prospective Studies
Risk Factors
Stroke / blood,  genetics,  mortality
Grant Support
Reg. No./Substance:

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