SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction
| Autor: | Yechiel Friedlander, Ronen Durst, Vardiella Meiner, Stephen M. Schwartz, David S. Siscovick, Gilli Erez, Eran Leitersdorf, Andrea S. Robertson |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Risk medicine.medical_specialty Adolescent Population Myocardial Infarction Polymorphism (computer science) Internal medicine Genotype Humans Protein Isoforms Medicine Myocardial infarction Risk factor education Genotyping Stroke education.field_of_study Polymorphism Genetic business.industry Intracellular Signaling Peptides and Proteins Case-control study Membrane Proteins Middle Aged medicine.disease Endocrinology Case-Control Studies Female Cardiology and Cardiovascular Medicine business Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | Atherosclerosis. 196:896-904 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2007.02.006 |
| Popis: | 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 18–49 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 for age 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. |
| Databáze: | OpenAIRE |
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