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Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

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The metabolically active form of vitamin D, 1,25-(OH)2D3, is involved in the regulation of insulin level. Because the serum group-specific component (Gc) binds vitamin D, it is worth knowing whether differences in basal insulin levels are associated with Gc genotype. Such differences would warrant further investigation to clarify whether selection maintains Gc polymorphism through differential risk of Gc genotypes to diseases that involve insulin. Blood samples were collected in a study designed to address issues in the etiology of non-insulin-dependent diabetes mellitus in Amerindians. Fasting insulin levels and Gc genotype (including subtypes of Gc1) were determined for 144 adult Dogrib Indians of the Northwest Territories, Canada. Hierarchical regression of log10 transformed fasting insulin on age and adiposity within each sex showed that age had no effect on insulin level, but adiposity as measured by the body mass index (BMI) had a very highly significant effect. Analysis of covariance of log10 fasting insulin by sex, by Gc genotype and with adjustment for the effects of the covariate, BMI, was very highly significant. All interaction terms in the model were nonsignificant. The only variable that had a significant effect after adjustment for the BMI was Gc genotype (F4,133 = 3.71; P = 0.007). Covariance analysis was repeated on a subset of the sample (124 people). The reduced data set excluded all individuals who had, on at least one occasion, abnormal response to oral glucose challenge [impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM]). Again, after correction for the effects of the BMI, only Gc genotype had a significant effect on fasting insulin level (F4,113 = 2.61; P = 0.040). Homozygotes for Gc 1F-1F had the lowest measures of fasting insulin.

The prevalence of diagnosed diabetes in several genetically closely related indigenous populations in the circumpolar arctic and subarctic regions of Russia, Alaska and Canada is compared. The age-standardized (to the IARC's hypothetical world population) prevalence ranged from 1.8/1000 among the Chukchi and Eskimo of Chukotka, 3.6 and 7.9/1000 among the Eskimos/Inuit of the Canadian Northwest Territories (NWT) and Alaska respectively, 7.1, 9.3 and 18.6/1000 among Athapaskan Indians in the NWT, Yukon and Alaska respectively, to a high of 22.7/1000 among the Aleuts in Alaska. All are below the US all-race prevalence of 23.5/1000 and far below the extreme high prevalence reported from many North American Indian tribes. As a group, such arctic and subarctic peoples have a much shorter and less intense history of European contact and acculturation. Environmental factors are also likely to be responsible for the current differences between these indigenous populations in the circumpolar region, assuming that they share susceptibility genes for diabetes inferred from their close genetic relationships based on markers in other loci. Formal surveys of glucose tolerance and potential risk factors such as diet, physical activity, obesity, insulin resistance and genetic admixture in the circumpolar region would improve knowledge of the aetiology of diabetes in genetically and culturally diverse human populations.