GENETIC ANALYSES OF GLUCOSE-TRANSPORTER GENES IN FRENCH NON-INSULIN-DEPENDENT DIABETIC FAMILIES

Impaired glucose-stimulated insulin secretion and impaired insulin-med iated glucose uptake are both prominent phenotypic features of non-ins ulin-dependent diabetes mellitus (NIDDM). Membrane proteins GLUT1 (Hep G2), 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 link age analyses between NIDDM and 10 polymorphic markers near GLUT1, GLUT 2 and GLUT4 genes in 79 multiplex French NIDDM families. Linkage analy ses were performed using both parametric (lodscore) and non-parametric (allele sharing among affected sib pairs) methods. No evidence was fo und for linkage between NIDDM and GLUT1, GLUT2 and GLUT4 regions, rega rdless of the methods or models used for analyses. Thus, these familia l linkage studies demonstrate that GLUT1, GLUT2 and GLUT4 loci did not contribute significantly to NIDDM in this cohort. The decreased expre ssion of glucose transporters observed in some NIDDM patients may he s econdary to other genetic or environmental defects.