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.

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.

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.

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.

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme participating in the metabolism of numerous pharmaceutical drugs and carcinogens found in tobacco smoke and diet. The NAT2 gene is highly polymorphic and several different allelic variants exist that determine the acetylator phenotype. In the course of our case-control study, we developed a new method based on fluorogenic allele-specific probes for analyzing the C282T and T341C polymorphisms of the NAT2 gene in 483 Finnish breast cancer patients and 482 healthy population controls. The slow NAT2 acetylation capacity-associated genotypes posed a somewhat increased overall breast cancer risk (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.01-1.73). This association was found to be confined to the advanced (stage III or IV) breast cancer (OR, 2.60; 95% CI, 1.29-5.24). When stratified by smoking habits, women who had smoked <5 pack-years and carried a NAT2 slow acetylator genotype were at a 2.6-fold (OR, 2.55; 95% CI, 1.01-6.48) risk of breast cancer. Moreover, women with the NAT2 slow acetylator genotype and low body mass index (BMI) (<25.4 kg/m2) were at somewhat increased risk of this malignancy (OR, 1.60; 95% CI, 1.07-2.39). Our results therefore suggest that NAT2 slow acetylator genotype may be an important modifier of environmentally induced breast cancer risk in Finnish women.

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme participating in the metabolism of numerous pharmaceutical drugs and carcinogens found in tobacco smoke and diet. The NAT2 gene is highly polymorphic and several different allelic variants exist that determine the acetylator phenotype. In the course of our case-control study, we developed a new method based on fluorogenic allele-specific probes for analyzing the C282T and T341C polymorphisms of the NAT2 gene in 483 Finnish breast cancer patients and 482 healthy population controls. The slow NAT2 acetylation capacity-associated genotypes posed a somewhat increased overall breast cancer risk (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.01-1.73). This association was found to be confined to the advanced (stage III or IV) breast cancer (OR, 2.60; 95% CI, 1.29-5.24). When stratified by smoking habits, women who had smoked <5 pack-years and carried a NAT2 slow acetylator genotype were at a 2.6-fold (OR, 2.55; 95% CI, 1.01-6.48) risk of breast cancer. Moreover, women with the NAT2 slow acetylator genotype and low body mass index (BMI) (<25.4 kg/m2) were at somewhat increased risk of this malignancy (OR, 1.60; 95% CI, 1.07-2.39). Our results therefore suggest that NAT2 slow acetylator genotype may be an important modifier of environmentally induced breast cancer risk in Finnish women.

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.

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.