title: High frequency of polymorphism but no mutations found in the GLUT1 glucose transporter gene in NIDDM and familial obesity by SSCP analysis.
abstract: To evaluate whether a structural defect in the human glucose transporter gene GLUT1 could be involved in the aetiology of insulin resistance, a key factor of non-insulin-dependent diabetes mellitus (NIDDM) and obesity, we performed single-strand conformation polymorphism (SSCP) analysis in 40 subjects (20 NIDDM patients and 20 subjects with familial obesity). The GLUT1 gene, which is involved in basal glucose transport in most tissues, consists of ten exons and encodes a 492 amino acid protein. Population studies have shown a strong association between the X1 allele of an XbaI restriction fragment length polymorphism of the GLUT1 gene and NIDDM. We therefore performed SSCP analysis in NIDDM subjects known to carry at least one X1 allele. Variant SSCP patterns were detected in exons 2, 4, 5 and 9. Sequence analysis of the SSCP variants revealed the presence, in all exons examined, of silent mutations consisting of single-nucleotide substitutions with no amino acid changes. Both NIDDM and obese patients showed a high frequency of polymorphism in the sequence (50% and 35%, respectively). We conclude that the GLUT1 gene is unlikely to play a role in the aetiology of NIDDM and obesity. However, the strong association between the GLUT1 gene and NIDDM, together with the recent family studies showing linkage between chromosome 1p and NIDDM warrant further studies on this chromosomal region.
authors.affiliation: Istituto II Clinica Medica, Policlinico Umberto I, University of Rome La Sapienza, Italy. baroni@caspur.it
authors.forename: M G
authors.initials: MG
authors.lastname: Baroni
authors.forename: M P
authors.initials: MP
authors.lastname: D'Andrea
authors.forename: F
authors.initials: F
authors.lastname: Capici
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
authors.forename: M G
authors.initials: MG
authors.lastname: Cavallo
authors.forename: F
authors.initials: F
authors.lastname: Fallucca
authors.forename: C
authors.initials: C
authors.lastname: Giovannini
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D005947:Glucose