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

Y. Jamshidi, S. B. Gooljar, H. Snieder, X. Wang, D. Ge, R. Swaminathan, T. D. Spector, S. D. O'Dell

Research output: Contribution to journalArticle

17 Scopus citations

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 languageEnglish (US)
Pages (from-to)e26-e33
JournalAtherosclerosis
Volume194
Issue number2
DOIs
StatePublished - Oct 1 2007

Keywords

  • Genetic susceptibility
  • LDL-cholesterol
  • Metabolic syndrome
  • PI3-kinase
  • SHP-2
  • apoB

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Jamshidi, Y., Gooljar, S. B., Snieder, H., Wang, X., Ge, D., Swaminathan, R., Spector, T. D., & O'Dell, S. D. (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