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Previous Volume 328:10-14 January 7, 1993 Number 1 Next

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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.

Methods and Results Using a human complementary DNA probe, the restriction enzyme XbaI, 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 XbaI polymorphism was due to a change of a single base in an intron.

Conclusions The XbaI 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.

Source Information

From the Fourth Department of Medicine (L.C.G., C.S.-J., A.E., E.W., J.E., A.F.-K., C.S.) and the Department of Biochemistry (M.K., P.N.-I., E.K.), Helsinki University, and the Finnish Red Cross Blood Transfusion Service (S.K.), both in Helsinki, Finland.

Address reprint requests to Dr. Groop at the Fourth Department of Medicine, Helsinki University Hospital, Unioninkatu 38, SF-00170 Helsinki, Finland.

Full Text of this Article

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Polymorphism of the Glycogen Synthase Gene and Non-Insulin-Dependent Diabetes Mellitus
Zouali H., Velho G., Froguel P., Kadowaki T., Kadowaki H., Yazaki Y., Groop L., Schalin-Jantti C., Lehto M.
Extract | Full Text  
N Engl J Med 1993; 328:1568-1569, May 27, 1993. Correspondence

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