例如:"lncRNA", "apoptosis", "WRKY"

An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels.

Circulation. 2018 Sep 25;138(13):1343-1355
May E Montasser 1 , Elizabeth A O'Hare 2 , Xiaochun Wang 1 , Alicia D Howard 1 , Rebecca McFarland 1 , James A Perry 1 , Kathleen A Ryan 1 , Kenneth Rice 3 , Cashell E Jaquish 4 , Alan R Shuldiner 1 , Michael Miller 5 , Braxton D Mitchell 6 , Norann A Zaghloul 1 , Yen-Pei C Chang 1
May E Montasser 1 , Elizabeth A O'Hare 2 , Xiaochun Wang 1 , Alicia D Howard 1 , Rebecca McFarland 1 , James A Perry 1 , Kathleen A Ryan 1 , Kenneth Rice 3 , Cashell E Jaquish 4 , Alan R Shuldiner 1 , Michael Miller 5 , Braxton D Mitchell 6 , Norann A Zaghloul 1 , Yen-Pei C Chang 1
+ et al

[No authors listed]

Author information
  • 1 Division of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
  • 2 The present affiliation for Dr O'Hare is Department of Biological Sciences, Towson University, MD.
  • 3 Department of Biostatistics, University of Washington, Seattle (K.R.).
  • 4 Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (C.E.J.).
  • 5 Division of Cardiovascular Medicine (M.M.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
  • 6 Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

摘要


BACKGROUND:Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease via its contribution to the development and progression of atherosclerotic lesions. Although the genetic basis of LDL-C has been studied extensively, currently known genetic variants account for only ≈20% of the variation in LDL-C levels. METHODS:Through an array-based association analysis in 1102 Amish subjects, we identified a variant strongly associated with LDL-C levels. Using a combination of genetic analyses, zebrafish models, and in vitro experiments, we sought to identify the causal gene driving this association. RESULTS:We identified a founder haplotype associated with a 15 mg/dL increase in LDL-C on chromosome 5. After recombination mapping, the associated region contained 8 candidate genes. Using a zebrafish model to evaluate the relevance of these genes to cholesterol metabolism, we found that expression of the transcribed pseudogene, APOOP1, increased LDL-C and vascular plaque formation. CONCLUSIONS:Based on these data, we propose that APOOP1 regulates levels of LDL-C in humans, thus identifying a novel mechanism of lipid homeostasis.

KEYWORDS: cholesterol, LDL, chromosome mapping, founder effect, genetics, pseudogenes