Impaired
glycogen synthesis after
insulin stimulation accounts for most of the
insulin resistance in patients with
non-insulin-dependent diabetes mellitus (
NIDDM). The
glycogen synthase gene (GYS1), which encodes the rate-limiting
enzyme for
glycogen synthesis, is a promising candidate gene for
NIDDM. Therefore, we screened all 16 exons of this gene by single-strand conformation polymorphism analysis in 40 patients with
NIDDM (age 67 +/- 2 years, body mass index 28.2 +/- 0.6 kg/m2) from Taipalsaari, eastern Finland. The Gly464Ser variant (exon 11) and a silent polymorphism TTC342TTT (exon 7) have been reported previously. In addition, we found a new variant Gln71His (exon 2) and a new
amino acid polymorphism Met416Val (exon 10). An additional sample of 65 patients with
NIDDM and 82 normoglycaemic men (age 54 +/- 1 years, body mass index 26.3 +/- 1.4 kg/m2) were screened. The allele frequency of the TTC342TTT silent substitution was 0.29 in both
NIDDM and normoglycaemic subjects. The Gln71His and Gly464Ser variants were found in 1 (1%) and 3 (3%) subjects, respectively, of the 105
NIDDM patients and in none of the 82 normoglycaemic men. The Met416Val polymorphism was found in 16 (15%) of the 105
NIDDM patients and in 14 (17%) of the 82 control subjects (all heterozygous). The Met416Val polymorphism was not associated with
insulin resistance in two groups of normoglycaemic subjects. In conclusion, the new Gln71His and Met416Val substitutions and other variants of the
glycogen synthase gene are unlikely to make a major contribution to
insulin resistance and
NIDDM in diabetic patients from eastern Finland.