title: Association between polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus.
abstract: BACKGROUND
  The storage of glucose as glycogen in skeletal muscle is frequently impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their nondiabetic relatives. Despite an intensive search for candidate genes associated with NIDDM, no data have been available on the gene coding for the key enzyme of this pathway, glycogen synthase.
  
  
  RESULTS
  Using a human complementary DNA probe, the restriction enzyme Xbal, and Southern blot analysis, we identified two polymorphic alleles, A1 and A2, in the glycogen synthase gene. The gene was localized to chromosome 19. The A1A2 or A2A2 genotype was found in 30 percent of 107 patients with NIDDM but in only 8 percent of 164 nondiabetic subjects without a family history of NIDDM (P < 0.001). The diabetic patients with the A2 allele had a stronger family history of NIDDM (P = 0.019), a higher prevalence of hypertension (P = 0.008), and a more severe defect in insulin-stimulated glucose storage (P = 0.001) than the diabetic patients with the A1 allele. The concentration of the glycogen synthase protein in biopsy specimens of skeletal muscle from the patients with the A2 allele was normal, however, suggesting that expression of the gene was unaltered. The Xbal polymorphism was due to a change of a single base in an intron.
  
  
  CONCLUSIONS
  The Xbal polymorphism of the glycogen synthase gene identifies a subgroup of patients with NIDDM characterized by a strong family history of NIDDM, a high prevalence of hypertension, and marked insulin resistance.
authors.affiliation: Fourth Department of Medicine, Helsinki University, Finland.
authors.forename: L C
authors.initials: LC
authors.lastname: Groop
authors.forename: M
authors.initials: M
authors.lastname: Kankuri
authors.forename: C
authors.initials: C
authors.lastname: Schalin-Jäntti
authors.forename: A
authors.initials: A
authors.lastname: Ekstrand
authors.forename: P
authors.initials: P
authors.lastname: Nikula-Ijäs
authors.forename: E
authors.initials: E
authors.lastname: Widén
authors.forename: E
authors.initials: E
authors.lastname: Kuismanen
authors.forename: J
authors.initials: J
authors.lastname: Eriksson
authors.forename: A
authors.initials: A
authors.lastname: Franssila-Kallunki
authors.forename: C
authors.initials: C
authors.lastname: Saloranta
mesh_terms: D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D016009:Chi-Square Distribution; D015342:DNA Probes; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006006:Glycogen Synthase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology; D011110:Polymorphism, Genetic
chemical_list: D001786:Blood Glucose; D015342:DNA Probes; D006006:Glycogen Synthase