Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_2450

Reference

Title : Resequencing genomic DNA of patients with severe hypertriglyceridemia (MIM 144650) - Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_2450
Author(s) : Wang J , Cao H , Ban MR , Kennedy BA , Zhu S , Anand S , Yusuf S , Pollex RL , Hegele RA
Ref : Arterioscler Thromb Vasc Biol , 27 :2450 , 2007
Abstract :

OBJECTIVE: The genetic determinants of severe hypertriglyceridemia (HTG; MIM 144650) in adults are poorly defined. We therefore resequenced 3 candidate genes, namely LPL, APOC2, and APOA5, to search for accumulation of missense mutations in patients with severe HTG compared with normolipidemic subjects. METHODS AND RESULTS: We resequenced >2 million base pairs of genomic DNA from 110 nondiabetic patients with severe HTG and determined the prevalence of coding sequence variants compared with 472 age- and sex-matched normolipidemic controls. We found: (1) heterozygous mutations (LPL p.Q-12E >11X, p.D25H, p.W86R, p.G188E, p.I194T and p.P207L; APOC2 p.K19T and IVS2-30G>A) in 10.0% of severe HTG patients compared with 0.2% of controls (carrier odds ratio [OR] 52, 95% confidence interval [CI] 8.6 to 319); and (2) an association of the APOA5 p.S19W missense variant with severe HTG (carrier OR 5.5 95% CI 3.3 to 9.1). Furthermore, either rare mutations or the APOA5 p.S19W variant were found in 41.8% of HTG subjects compared with 8.9% of controls (carrier OR 7.4, 95% CI 4.5 to 12.0). Also, heterozygotes for rare mutations had a significantly reduced plasma triglyceride response to fibrate monotherapy. CONCLUSIONS: Both common and rare DNA variants in candidate genes were found in a substantial proportion of severe HTG patients. The findings underscore the value of candidate gene resequencing to understand the genetic contribution in complex lipoprotein and metabolic disorders.

PubMedSearch : Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_2450
PubMedID: 17717288
Gene_locus related to this paper: human-LPL

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Citations formats

Wang J, Cao H, Ban MR, Kennedy BA, Zhu S, Anand S, Yusuf S, Pollex RL, Hegele RA (2007)
Resequencing genomic DNA of patients with severe hypertriglyceridemia (MIM 144650)
Arterioscler Thromb Vasc Biol 27 :2450

Wang J, Cao H, Ban MR, Kennedy BA, Zhu S, Anand S, Yusuf S, Pollex RL, Hegele RA (2007)
Arterioscler Thromb Vasc Biol 27 :2450