POLYMORPHISMS OF THE HUMAN HEXOKINASE-II GENE - LACK OF ASSOCIATION WITH NIDDM AND INSULIN-RESISTANCE

Skeletal muscle and adipose tissue hexokinase II is a promising candid ate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insul in resistance. Therefore, we investigated the association of alleles a t four polymorphic loci in this gene with NIDDM and insulin resistance in 110 Finnish diabetic patients with NIDDM and in 97 Finnish control subjects with normal glucose tolerance and a negative family history of diabetes. The four polymorphic nucleotide substitutions (silent) in the coding region of the hexokinase II gene were: GAC 251 GAT (exon 7 ), AAC 692 AAT and CCG 734 CCC (exon 15), and CTG 766 CTA (exon 16). A llele frequencies of each of these polymorphisms did not differ betwee n patients with NIDDM and control subjects. In addition, subjects who were homozygous for the less frequent allele of each of the four polym orphisms had a similar degree of insulin resistance, as determined by the euglycaemic clamp technique, as did the subjects who were homozygo us for the common allele in both control subjects and in patients with NIDDM. In conclusion, polymorphisms in the hexokinase II gene are not associated with the risk of NIDDM or insulin resistance in the Finnis h population.