EVIDENCE FOR LINKAGE BETWEEN A REGION ON CHROMOSOME 1P AND THE ACUTE INSULIN-RESPONSE IN PIMA-INDIANS

A low acute insulin response (AIR) is a predictor of non-insulin-depen dent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. We h ave initiated a search for regions of the genome linked with the AIR u sing sib-pair linkage analysis as a first step in identifying genes th at are determinants of this phenotype. Eighteen short tandem-repeat po lymorphisms from chromosome 1 were genotyped in over 900 Pima Indians and tested for linkage with NIDDM and in a subset of Pima Indians for linkage with ATR. The anonymous DNA marker D1S198 on chromosome 1p was linked with AIR (P = 0.000056) in 175 sib pairs from 60 families, all with normal glucose tolerance, but no linkage was observed between D1 S198 and NIDDM (P = 0.44, 996 sib pairs). Additional markers genotyped on chromosome 1 did not show linkage with AIR or NIDDM. This study in dicates that a locus on chromosome 1p may be a determinant of the phen otypic variation seen in the ATR.