SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction

被引:17
作者
Friedlander, Yechiel [1 ]
Schwartz, Stephen M. [2 ,3 ]
Durst, Ronen
Meiner, Vardiella [4 ]
Robertson, Andrea S. [2 ]
Erez, Gilli [5 ]
Leitersdorf, Eran [5 ]
Siscovick, David S. [2 ,3 ]
机构
[1] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel
[2] Dept Med, Cardopvasc Hlth Res Unit, Washington, DC USA
[3] Univ Washington, Dept Epidemiol, Washington, DC USA
[4] Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel
[5] Hadassah Univ Hosp, Ctr Res Prevent & Treatment Atherosclerosis, Dept Med B, IL-91120 Jerusalem, Israel
关键词
myocardial infarction; early-onset; SCAP; SREBP; genetic polymorphism; gene-gene interaction;
D O I
10.1016/j.atherosclerosis.2007.02.006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Cholesterol metabolism is mediated, in part, by the sterol-regulatory element binding proteins (SREBPs) that are activated by a SREBP cleavage-activating protein (SCAP). We examined whether coding variations in the interacting domains of both genes, are related to early-onset MI risk in a population-based case-control study from western Washington State. Methods: Cases were 257 women, aged 18-59 years, and 320 men, aged 18-19 years, with first acute non-fatal MI; controls were 353 women and 311 men, similar in age, identified from the community who had no history of clinical CHD or stroke. Genotyping of the SREBF-2 G1784C polymorphism (SREBP-2-595A/G isoforms), and the SCAP A2386G polymorphism (SCAP-796I/V isoforms), were performed. Results: After adjustment forage and race, the SREBP-2-595A isoform was associated with increased MI risk among men (OR=1.63, 95% CI=1.26-2.12). In contrast, there was little evidence for an association among women in a multiplicative model. However, compared to SREBP-2-595G homozygotes, homozygote women for the SREBP-2-595A isoform were at nearly two-fold increased risk (OR=1.95, 95% CI=1.07-3.54). Overall. SCAP genotypes were neither associated with MI in men nor in women. However, in men, SCAP genotypes were found to modify the association between SREBF-2 and MI (p-value for interaction = 0.01). Conclusion: The SREBP-2-595A isoform was associated with an increased risk of early-onset MI in U.S. men. The SCAP polymorphism appeared to modify the associations of SREBF-2 genotype with MI risk among men. These novel findings require confirmation in other populations. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:896 / 904
页数:9
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