Genetic analyses of glucose transporter genes in French non-insulin-dependent diabetic families.
Impaired glucose-stimulated insulin secretion and impaired insulin-mediated glucose uptake are both prominent phenotypic features of non-insulin-dependent diabetes mellitus (NIDDM). Membrane proteins GLUT1 (HepG2), GLUT2 (liver/islet), and GLUT4 (muscle/adipose tissue) facilitate glucose uptake into cells, and their genes are candidates for NIDDM. To assess their role in primary defects of diabetes, we performed linkage analyses between NIDDM and 10 polymorphic markers near GLUT1, GLUT2 and GLUT4 genes in 79 multiplex French NIDDM families. Linkage analyses were performed using both parametric (lodscore) and non-parametric (allele sharing among affected sib pairs) methods. No evidence was found for linkage between NIDDM and GLUT1, GLUT2 and GLUT4 regions, regardless of the methods or models used for analyses. Thus, these familial linkage studies demonstrate that GLUT1, GLUT2 and GLUT4 loci did not contribute significantly to NIDDM in this cohort. The decreased expression of glucose transporters observed in some NIDDM patients may be secondary to other genetic or environmental defects.
Lesage
S
S
CNRS EP10, Institut Pasteur de Lille, France.
Zouali
H
H
Vionnet
N
N
Philippi
A
A
Velho
G
G
Serradas
P
P
Passa
P
P
Demenais
F
F
Froguel
P
P
D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D006528:Carcinoma, Hepatocellular; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005602:France; D008040:Genetic Linkage; D005819:Genetic Markers; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D009124:Muscle Proteins; D012150:Polymorphism, Restriction Fragment Length; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D005819:Genetic Markers; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human