HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db07-0558v1 57/5/1427    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Andersen, G. Articles by Pedersen, O. Search for Related Content PubMed PubMed Citation Articles by Andersen, G. Articles by Pedersen, O. Social Bookmarking                What's this?

AHSG tagSNPs associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 Danish whites

¹Steno Diabetes Center, Gentofte, Denmark
²Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
³Faculty of Health Science, University of Aarhus, Aarhus, Denmark

Objective: The gene encoding the 2 Heremans-Schmid glycoprotein, AHSG, is a credible biological and positional candidate gene for type 2 diabetes and the metabolic syndrome, and previous attempts to relate AHSG variation with type 2 diabetes and obesity in Swedish and French Caucasians have been largely successful. We related seven frequent AHSG tagSNPs to a range of metabolic traits including type 2 diabetes, obesity, and dyslipidemia.

Research Design And Methods: The polymorphisms were genotyped in 7,683 Danish whites using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, providing a statistical power of more than 99% to replicate previous findings. Data were analysed in case-control and haplotype settings, and quantitative metabolic traits were examined for association. Moreover, epistatic effects between AHSG variants and IRS1 and ADRB2 polymorphisms were investigated.

Results: The –469T>G (rs2077119) and IVS6+98C>T (rs2518136) polymorphisms were associated with type 2 diabetes (P=0.007 and P=0.006, respectively, or P_corr=0.04 and P_corr=0.03 following correction for multiple hypothesis testing), and in a combined analysis of the present and a previous study –469T>G remained significant (OR 0.90 [0.84-0.97], P=0.007). Furthermore, two AHSG haplotypes were associated with dyslipidemia (P=0.003, P_corr=0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-OGTT serum insulin release (P=0.02, P_corr=0.1 for fasting and P=0.04, P_corr=0.2 for area under the insulin curve) and improved insulin sensitivity estimated by the homeostasis model assessment of insulin resistance (9.0 mmol/l·pmol/l vs. 8.6 mmol/l·pmol/l, P=0.01, P_corr=0.06). Indications of epistatic effects of AHSG variants with the IRS1 Gly971Arg polymorphism were observed for fasting serum triglyceride concentrations.

Conclusions: Based upon present and previous findings common variation in AHSG may contribute to the inter-individual variation in metabolic traits.

Key Words: obesity • dyslipidemia • genetics • association • haplotype

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?