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Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2) glucose transporter in Japanese subjects

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Summary

The beta-cell/liver glucose transporter (GLUT2) gene was screened for mutations using single-strand conformation polymorphism analysis (SSCP) in 30 Japanese subjects with non-insulin dependent diabetes mellitus (NIDDM). Analysis of all exons and adjacent intron regions identified six SSCP polymorphisms, three of which resulted in amino acid substitutions: V101I, T110I and G519E. The V101I and G519E substitutions represent new polymorphisms in this gene. The six polymorphisms were observed in both NIDDM and control groups and there were no significant differences in allele frequencies between groups. A portion of the insulin receptor substrate 1 gene in 30 NIDDM subjects and in normal control subjects was also screened for mutations. Two SSCP variants that change the sequence of the protein, δS686/687 (deletion of the codons for serine-686 and 687) and G972R, were identified in two different NIDDM subjects, both whom were also heterozygous for the V101I polymorphism in GLUT2. The GLUT2 and IRS1 amino acid polymorphisms did not show a simple pattern of co-inheritance with NIDDM in the families of these subjects suggesting that neither polymorphism is sufficient to cause NIDDM but may increase diabetes-susceptibility through their interaction with other loci and environmental factors.

Abbreviations

NIDDM:

Non-insulin-dependent diabetes mellitus

GLUT2:

glucose transporter 2

IRS1:

insulin receptor substrate-1

SSCP:

single-stranded conformation polymorphism

PCR:

polymerase chain reaction

Thr:

threonine

Phe:

phenylalanine

Ala:

alanine

Ser:

serine

Ile:

isoleucine

Val:

valine

Gly:

glycine

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Correspondence to Dr. H. Makino.

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Shimada, F., Makino, H., Iwaoka, H. et al. Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2) glucose transporter in Japanese subjects. Diabetologia 38, 211–215 (1995). https://doi.org/10.1007/BF00400096

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Key words

  • Diabetes
  • glucose transporter
  • insulin receptor substrate-1
  • insulin
  • genetics