LINKAGE ANALYSIS OF THE GENETIC-MARKERS OF THE CANDIDATE GENES WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS IN CHINESE FAMILIES

Objective To explore the relationship between the genetic markers of t he candidate genes (insulin receptor, glucose transporter 2 and glucok inase) and non-insulin dependent diabetes mellitus (NIDDM) in Chinese pedigrees. Methods Genomic DNA of 87 members in 12 Chinese NIDDM pedig rees was amplified using PCR technique. Denaturing polyacrylamide gel electrophoresis was applied to detect short tandem repeat polymorphism s. The linkage program was used under the models of autosomal dominant and recessive. The individuals with impaired glucose tolerance (IGT) of age less than or equal to 45 and age >45 were counted as affected a nd unknown status respectively. Results Linkage of insulin receptor ge ne and NIDDM was strongly and significantly rejected with total LOD sc ore of -infinity (theta = 0.000). Linkage analysis of glucose transpor ter 2 gave the result with total LOD score of 2.646 (theta = 0.000) in 4 pedigrees. Linkage of glucokinase and NIDDM was of significance wit h total LOD score reaching 3. 150 in the integration of 6 pedigrees. C onclusions Mutations in or near the insulin receptor gene are unlikely to be the major cause of inherited predisposition to NIDDM in Chinese pedigrees that are related in this study, not excluding the principal role in the other Chinese or populations, while the mutations/variati ons near or at the glucose transporter 2 gene locus might be something of the cause, which needs more data to be ascertained, of familiar NI DDM in Chinese pedigrees. However, the variations in or near the gluco kinase gene might play a dominant role in the development of NIDDM in some Chinese and represent a subgroup of common NIDDM.