Abstract
Insulin regulates apoB metabolism via activation of PI3K or regulation of MTP via MAPK/ERK signalling. SHP-2 enhances both pathways through increased IRS-1 phosphorylation. We hypothesized that variants in the SHP-2 gene PTPN11 and PI3K p85alpha subunit gene PIK3R1 may influence fasting levels of plasma apoB and/or LDL cholesterol. We tested association of tagging SNPs (tSNPs) in each gene with serum lipids in a large sample of unselected population-based Caucasian female twins (n = 2771, mean age 47.4 ± 12.5 years) and then tested interaction between tSNPs in determining apoB and LDL levels. PTPN11 tSNP rs11066322 was associated with apoB (P = 0.007) and rs11066320 was associated with LDL cholesterol (P = 0.016). PIK3R1 tSNP rs251406 was associated with apoB (P = 0.0003) and rs706713 was associated with LDL cholesterol (P = 0.009). PTPN11 tSNP rs11066322 interacted with PIK3R1 tSNP rs251406 in determining serum apoB levels (P = 0.012) and with PIK3R1 tSNP rs40318 in determining LDL cholesterol levels (P = 0.009). Association of single tSNPs with both apoB and LDL cholesterol as well as interactions between the two genes suggest that variants influencing SHP-2 activity may modulate the acute pathway by which insulin regulates these lipids.
Original language | English (US) |
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Pages (from-to) | e26-e33 |
Journal | Atherosclerosis |
Volume | 194 |
Issue number | 2 |
DOIs | |
State | Published - Oct 2007 |
Keywords
- Genetic susceptibility
- LDL-cholesterol
- Metabolic syndrome
- PI3-kinase
- SHP-2
- apoB
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine