title: Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia.
abstract: OBJECTIVE
  Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) underlie osteoporosis-pseudoglioma syndrome. Animal models implicate a role for LRP5 in lipid and glucose homeostasis. The objective was to evaluate metabolic consequences of LRP5 mutations in humans.
  
  
  METHODS
  Thirteen Finnish individuals with homozygous or heterozygous LRP5 mutations were assessed for bone health, glucose and lipid metabolism, and for serum serotonin concentration. Results were compared with findings in family members without mutations.
  
  
  METHODS
  Bone mineral density (BMD), vertebral morphology, oral and intravenous glucose tolerance tests, lipid profile and serum serotonin concentrations.
  
  
  RESULTS
  Two individuals were homozygous for R570W, one compound heterozygous for R570W and R1036Q, and 10 were heterozygous (six for R570W, three for R1036Q and one for R925C). Subjects with two LRP5 mutations had multiple spinal fractures and low BMD. Subjects with one mutation had significantly lower median lumbar spine (P = 0.004) and femoral neck (P = 0.005) BMD Z-scores, and more often vertebral fractures than the 18 individuals without mutations. Of the 12 subjects with LRP5 mutation six had diabetes and one had impaired glucose tolerance. Intravenous glucose tolerance tests suggested impaired beta-cell function; no insulin resistance was observed. Prevalence of hypercholesterolaemia was similar in mutation positive and negative subjects. Serum serotonin concentrations showed a trend towards higher concentrations in subjects with LRP5 mutation.
  
  
  CONCLUSIONS
  We found high prevalence of osteoporosis and abnormal glucose metabolism in subjects with LRP5 mutation(s). Further studies are needed to establish the role of LRP5 in glucose and lipid metabolism.
authors: Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.
authors: Anne
authors: A
authors: Saarinen
authors: Tero
authors: T
authors: Saukkonen
authors: Tero
authors: T
authors: Kivelä
authors: Ulla
authors: U
authors: Lahtinen
authors: Christine
authors: C
authors: Laine
authors: Mirja
authors: M
authors: Somer
authors: Sanna
authors: S
authors: Toiviainen-Salo
authors: William G
authors: WG
authors: Cole
authors: Anna-Elina
authors: AE
authors: Lehesjoki
authors: Outi
authors: O
authors: Mäkitie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015519:Bone Density / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D005910:Glioma / Q000235:genetics; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D050356:Lipid Metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010024:Osteoporosis / Q000235:genetics*; D013577:Syndrome
chemical_list: D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5