NO EVIDENCE FOR MUTATIONS IN A PUTATIVE BETA-CELL ATP-SENSITIVE K+ CHANNEL SUBUNIT IN MODY, NIDDM, OR GDM

The beta-cell ATP-sensitive K+ (K-ATP) channel has a major role in glu cose-induced insulin secret;ion, Screening the entire coding sequence of the gene for a putative beta-cell K-ATP channel subunit, K-ATP2, wi th single-strand conformation polymorphism did not show any mutations associated with diabetes in white Caucasian diabetic patients, includi ng five pedigrees with maturity onset diabetes of the young (MODY), 25 patients with noninsulin-dependent diabetes mellitus (NIDDM) selected for marked beta-cell deficiency, 25 selected for mild diabetes presen ting before age 50 years with fasting plasma glucose levels <10 mmol/l , 25 unselected NIDDM patients, and 25 subjects with gestational diabe tes mellitus (GDM) and subsequent raised fasting plasma glucose, In fi ve large MODY pedigrees, linkage analysis with simple tandem-repeat po lymorphisms (STRPs) near the K-ATP2 gene excluded linkage. In a popula tion association study, no linkage disequilibrium for the STRP was fou nd between 237 unselected white Caucasian NIDDM patients and 104 geogr aphically matched and age-matched white Caucasian nondiabetic subjects , In addition, two silent polymorphisms were found with similar freque ncy in nondiabetic and diabetic subjects. Mutations in the gene for K- ATP2 are unlikely to be a major cause of MODY, NIDDM or GDM.