POLYMORPHISMS AT THE GLUT2 (BETA-CELL LIVER) GLUCOSE TRANSPORTER GENE AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM) - ANALYSIS IN AFFECTED PEDIGREE MEMBERS

The precise genetic defects underlying the etiology of non-insulin-dependent diabetes mellitus (NIDDM) have yet to be identified. The beta-cell/liver glucose transporter gene GLUT2 represents a good candidate for the etiology of the disease, being involved in the glucose signalling for beta-cell insulin release. Population association studies of the GLUT2 gene in NIDDM have so far yielded controversial results. In order to determine the possible contribution of this gene to the inheritance of NIDDM, we have employed a new approach, where two polymorphic markers of the GLUT2 locus, detected with the restriction enzyme Taq-1, were examined for linkage with the disease in a group of 22 Italian pedigrees with affected members (n = 50). Departure from independent segregation between markers and disease was analyzed by the Affected-Pedigree-Members (APM) statistical method. Furthermore, association analysis between the Taq-1 RFLPs at the GLUT2 locus and NIDDM was performed in a group of diabetics with a strong family history, comprising the 22 probands and 23 other diabetics with an affected first-degree relative. The results indicate that there was no segregation distortion between the Taq-1 markers of the GLUT2 gene and the disease in the pedigrees examined. Also, no significant difference in genotype distribution, haplotype and allele frequencies was found between diabetics and controls for the two Taq-1 RFLPs. We conclude that genetic variation at the GLUT2 transporter gene is unlikely to contribute in a major way to the inheritance for NIDDM in this Italian population.