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AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects.

Abstract：

OBJECTIVE:The gene encoding the alpha2 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 tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia. RESEARCH DESIGN AND METHODS:The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic discrimination or chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, providing a statistical power of >99% to replicate previous findings. Data were analyzed in case-control and haplotype settings, and quantitative metabolic traits were examined for association. Moreover, epistatic effects between AHSG variants and insulin receptor substrate-1 (IRS1) and beta-2-adrenergic receptor 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, respectively, following correction for multiple hypothesis testing), and in a combined analysis of the present and a previous study -469T>G remained significant (odds ratio 0.90 [95% CI 0.84-0.97]; P = 0.007). Furthermore, two AHSG haplotypes were associated with dyslipidemia (P = 0.003 and P(corr) = 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-oral glucose tolerance test 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 vs. 8.6 mmol x l(-1) x pmol(-1) x l(-1); 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 on present and previous findings, common variation in AHSG may contribute to the interindividual variation in metabolic traits.

journal_name

Diabetes

journal_title

Diabetes

authors

Andersen G,Burgdorf KS,Sparsø T,Borch-Johnsen K,Jørgensen T,Hansen T,Pedersen O

doi

10.2337/db07-0558

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

1427-32

issue

eissn

0012-1797

issn

1939-327X

pii

db07-0558

journal_volume

pub_type

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AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects.