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SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL cholesterol levels in normal women.

Jamshidi, Y; Gooljar, SB; Snieder, H; Wang, X; Ge, D; Swaminathan, R; Spector, TD; O'Dell, SD (2007) SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL cholesterol levels in normal women. Atherosclerosis, 194 (2). e26 - e33. https://doi.org/10.1016/j.atherosclerosis.2006.12.013
SGUL Authors: Jamshidi, Yalda

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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.

Item Type: Article
Additional Information: PMCID: PMC2084489
Keywords: Adult, Apolipoproteins B, Cholesterol, LDL, Cohort Studies, Female, Genotype, Humans, Middle Aged, Phosphatidylinositol 3-Kinases, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Twins
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Atherosclerosis
Dates:
DateEvent
October 2007Published
PubMed ID: 17214991
Web of Science ID: 17214991
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URI: http://openaccess.sgul.ac.uk/id/eprint/13
Publisher's version: https://doi.org/10.1016/j.atherosclerosis.2006.12.013

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