GLUCOKINASE GENE IN GESTATIONAL DIABETES-MELLITUS - POPULATION ASSOCIATION STUDY AND MOLECULAR SCANNING

Mutations of the glucokinase gene result in early-onset familial Type 2 (non-insulin-dependent) diabetes mellitus, and several members of th e mutant glucokinase kindreds were originally diagnosed as having gest ational diabetes. This study examined the glucokinase gene in 270 Amer ican Black women, including 94 with gestational diabetes whose diabete s resolved after pregnancy (gestational diabetes only), 77 with gestat ional diabetes who developed Type 2 diabetes after pregnancy (overt di abetes), and 99 normal control subjects who were recruited during the peripartum period. Two simple sequence repeat polymorphisms flanking e ither end of the glucokinase gene were evaluated. No association was f ound between glucokinase alleles and gestational diabetes only or over t diabetes, after adjustment for multiple comparisons. To detect singl e base changes, all 11 exons and proximal islet and liver promoter reg ions were examined by polymerase chain reaction plus single-stranded c onformational polymorphism analysis in 45 gestational diabetes only pa tients who had not yet developed Type 2 diabetes. Nine coding region v ariants were identified: Ala(11) (GCC) to Thr(11) (ACC) in islet exon 1, and 8 variants either in untranslated regions or in the third base of a codon. Four variant sites were found in introns, but none in spli cing consensus sequences. Analysis of the promoter regions revealed tw o common variants, G-->A at islet - 30 (24%), and G-->A at liver - 258 (42%). The frequencies of the promoter variants, determined by allele specific polymerase chain reaction analysis, did not differ among the three groups. Thus, no significant coding sequence glucokinase mutati ons were found in 90 alleles from 45 patients with gestational diabete s. Further studies will be required to rule out a minor role of the ne wly-described promoter region variants as susceptibility factors in th is disorder.