title: NAT2 polymorphism associated with plasma glucose concentration in Canadian Oji-Cree.
abstract: The prevalence of type 2 diabetes in the Oji-Cree of Northern Ontario is among the highest of any population in the world. We previously demonstrated that markers D8S264 and D22S683 were both linked and associated with type 2 diabetes in the Oji-Cree. Among the possible candidate genes for type 2 diabetes and related traits on chromosomes 8p and 22q were NAT2 and CYP2D6, respectively. We thus explored the possible association of NAT2 and CYP2D6 alleles and diabetes-related traits in a sample of 112 Oji-Cree subjects with type 2 diabetes and 481 Oji-Cree subjects without type 2 diabetes. We found no difference in the allele and genotype frequencies of the NAT2 G191A, C282T, C481T, G590A, A803G and G857A, and the CYP2D6 G1934A polymorphisms between Oji-Cree subjects with and without type 2 diabetes. However, we found a significant association between the NAT2 C282T polymorphism and plasma fasting glucose concentration. Specifically, NAT2 282T/T homozygotes had significantly higher plasma fasting glucose than 282C/C homozygotes, and heterozygotes had intermediate levels of this trait. Thus, variation in NAT2 or CYP2D6 was not associated with the presence of type 2 diabetes, and would not be causative for this phenotype in Oji-Cree. However, NAT2 might be a 'modifier gene' affecting the level of glycaemia in non-diabetic subjects.
authors.affiliation: Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ontario, Canada. robert.hegele@rri.on.ca
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: K
authors.initials: K
authors.lastname: Kwan
authors.forename: S B
authors.initials: SB
authors.lastname: Harris
authors.forename: A J
authors.initials: AJ
authors.lastname: Hanley
authors.forename: B
authors.initials: B
authors.lastname: Zinman
authors.forename: H
authors.initials: H
authors.lastname: Cao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007198:Indians, North American; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009864:Ontario; D011110:Polymorphism, Genetic
chemical_list: D001786:Blood Glucose; D019389:Cytochrome P-450 CYP2D6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human