Aims: To establish the impact on the insulin resistance syndrome of the intron 14 Xba1-polymorphism in human muscle glycogen synthase (GYS1).
Methods: Parameters related to the insulin resistance syndrome were measured in 244 monozygotic twins and 322 dizygotic twins with or without impaired glucose tolerance. In addition a standard oral glucose tolerance test (OGTT) was performed. The twins were genotyped for Xba1-polymorphism in GYS1 intron 14.
Results: The allele frequency of Xba1 non-cutters (A1) was 0.95 and of cutters (A2) was 0.05. Of the 566 twins examined, 90.0% had the genotype A1A1 and the remainder had the genotype A1A2. No A2A2-genotypes were detected. In 11 genotypic discordant dizygotic twin pairs the insulin resistance was significantly increased in the twins carrying the A1A2 genotype regardless of sex (HOMA index 1.81 (A1A1) vs. 2.57 (A1A2), P < 0.05). Diastolic blood pressure was increased in female carriers of the A2-allele with impaired glucose tolerance or Type 2 diabetes mellitus (79 +/- 1 vs. 94 +/- 4 mmHg, P < 0.01). Apart from a marginal increased waist-to-hip ratio, no other elements of the insulin resistance syndrome were associated with the polymorphism.
Conclusions: The Xba1-polymorphism of the human muscle glycogen synthase gene is correlated to insulin resistance and to diastolic blood pressure. The polymorphism does not involve any known transcription factor or any structural change in GYS1, and these correlations are therefore most probably caused by linkage to other functional polymorphisms in GYS1 or other gene polymorphisms on chromosome 19.