Common INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle age.

 
TitleCommon INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle age.
Publication TypeJournal Article
Year of Publication2010
AuthorsFornage, M, Papanicolaou, G, Lewis, CE, Boerwinkle, E, Siscovick, DS
JournalMetabolism
Volume59
Issue8
Pagination1084-91
Date Published2010 Aug
ISSN1532-8600
KeywordsAdolescent, Adult, Age Factors, Body Mass Index, Body Size, Cholesterol, HDL, Cross-Sectional Studies, Female, Humans, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Polymorphism, Single Nucleotide, Young Adult
Abstract

Insulin-induced gene 2 (INSIG2) plays an important role in the regulation of cholesterol and fatty acids synthesis. A polymorphism, rs7566605, located 10 kilobases upstream of the INSIG2 gene, was identified in a genomewide association study of obesity. We conducted an association study of 12 INSIG2 tag-single nucleotide polymorphisms with longitudinal measures of body size (body mass index and waist circumference) and lipid metabolism (plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides levels). We investigated their interaction with age in 4304 Coronary Artery Risk Development in Young Adults participants (49.5% blacks, 50.5% whites) followed prospectively for 20 years. rs7566605 was not associated with variation in body size or lipid metabolism at any age in either racial group. However, rs1352083 and rs10185316 were associated with age-related decline in high-density lipoprotein cholesterol in whites (P = .0005 and .04, respectively). A similar trend was observed in blacks who consistently maintained a body mass index less than 25 kg/m(2) over the study period. These data support a role of INSIG2 sequence variation in the regulation of cholesterol metabolism.

DOI10.1016/j.metabol.2009.11.005
Alternate JournalMetab. Clin. Exp.
PubMed ID20045156
PubMed Central IDPMC2888786
Grant ListR01 HL084099-01A1 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
R01-HL69126 / HL / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
R01 HL084099-03 / HL / NHLBI NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
R01 HL084099 / HL / NHLBI NIH HHS / United States
R01 HL084099-02 / HL / NHLBI NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
R01 HL069126 / HL / NHLBI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States