کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2894459 | 1172435 | 2007 | 8 صفحه PDF | دانلود رایگان |
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.
Journal: Atherosclerosis - Volume 194, Issue 2, October 2007, Pages e26–e33