This study confirms a low frequency of multiple sclerosis (MS) among Sami. Only 12 Sami with a diagnosis of MS were identified in the Norwegian Sami population, which represents a significantly lower prevalence of MS in Sami (30/10(5)) compared with other Norwegians (73-164/10(5)). The clinical characteristics as well as the results of human leukocyte antigen (HLA)-DRB1 and -DQB1 typing of the Sami MS patients are reported, showing that three (27%) of the Sami MS patients carried the MS-associated HLA-DRB1*15-DQB1*06 haplotype. Interestingly, the DRB1*15-DQB1*06 haplotype had a significantly reduced frequency among Sami controls (0.086) compared with non-Sami Norwegian controls (0.163) (P(corrected) = 0.015). The low frequency of the disease-associated DRB1*15-DQB1*06 haplotype in the Sami population may contribute to the low prevalence of MS in Sami, in addition to other yet unidentified genetic and environmental factors.

A number of metabolic pathways are subject to both genetic polymorphism and interethnic differences. A catabolic pathway of 6-mercaptopurine, red blood cell (RBC) thiopurine methyltransferase (TPMT) activity showed genetic polymorphism in Caucasians, but variation according to ethnicity has not been studied. We investigated if red blood cell thiopurine methyltransferase was subject to interethnic variation in a Saami (Lappish; n = 36) and a Caucasian population (n = 50). The Saami population sample had 29% higher thiopurine methyltransferase activity, 17.0 +/- 3.3 U/ml red blood cell compared with the Caucasian population sample, 13.1 +/- 2.9 U/ml red blood cell (p much less than 0.001). Probit plots and frequency distribution histograms supported bimodality consistent with genetic polymorphism in both study populations. Differences in chronic diseases, drug consumption, age, or gender could not explain the interethnic difference in red blood cell thiopurine methyltransferase activity. The higher red blood cell thiopurine methyltransferase activity in the Saami population group indicates that these subjects may require higher dosages of thiopurine drugs than Caucasians.

Thiopurine S-methyltransferase (TPMT) activity exhibits genetic polymorphism. The purpose of this investigation was to identify TPMT mutant alleles in the Saami population as a basis of developing genotyping tests for prediction of TPMT activity. The most predominant allele in Saamis (n = 194) was the TPMT*3C allele (A719G mutation) representing 92% of the mutant alleles, with an estimated allelic frequency of 3.3%. The most frequent allele in Caucasians (n = 66) living in the same geographic area was the TPMT*3A (A719G and G460A mutations) representing 91% of the mutant alleles, with an estimated allelic frequency of 3.4%. A test for one mutation, A719G, may prospectively identify more than 90% of the Saami individuals who require reduction in thiopurine dose to avoid hematopoietic toxicity. In a Norwegian population, comprising both the major Caucasian population and a minor Saami population, the same genotyping tests (eg, tests for the A719G and G460A mutations) may be used.

Summary Receptors for the Fc domain of IgG (FcγR) play a critical role in linking cellular and humoral immunity. The various FcγR genotypes may contribute to differences in infectious and immune‐related diseases in various ethnic populations. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and differ ethnically from the Norwegians. The distribution of various immune‐related diseases has been reported to differ between Sami and Norwegians. This is the first study to evaluate the distribution of FcγR polymorphisms in a Sami population. Two hundred Samis were genotyped for polymorphisms in the FcγRIIA, FcγRIIIA and FcγRIIIB genes. The genotype and allele frequencies were compared with those of 272 healthy Norwegians. The Sami and Norwegian FcγRIIA, FcγRIIIA and FcγRIIIB genotypes differed significantly. The Samis had higher frequencies of the FcγRIIa‐H/H131, FcγRIIIa‐F/F158 and FcγRIIIb‐NA1/NA1 genotypes. The FcγR genotypes were non‐randomly distributed in both populations. These findings may be important for the prevalence of autoimmune and infectious diseases in the two populations.

This study reports extensive genomic data for both human leukocyte antigen (HLA) class I and II loci in Norwegian Sami, a native population living in the northwest of Europe. The Sami have a distinct culture and their own languages, which belong to the Uralic linguistic family. Norwegian Sami (n = 200) were typed at the DNA level for the HLA-A, -C, -B, -DRB1 and -DQB1 loci, and compared with a non-Sami Norwegian population (n = 576). The two populations exhibited some common genetic features but also differed significantly at all HLA loci. The most significantly deviating allele frequencies were an increase of HLA-A*03, -B*27, -DRB1*08 and -DQB1*04 and a decrease of HLA-A*01, C*01, -DRB1*04 and -DQB1*02 among Sami compared with non-Sami Norwegians. The Sami showed no deviation from Hardy-Weinberg equilibrium. The hypothesis of selective neutrality was rejected at all loci except for the A- and C- loci for the Sami. HLA haplotype frequencies also differed between the two populations. The most common extended HLA haplotypes were A*02-B*27-C*01-DR*08-DQB1*04 in the Sami and A*01-B*08-C*07-DR*03-DQB1*02 in the other Norwegians. Genetic distance analyses indicated that the Norwegian Sami were highly differentiated from other Europeans and were most closely related to Finns whose language also belongs to the Uralic linguistic family. In conclusion, the Norwegian Sami and the non-Sami Norwegians were significantly different at all HLA loci. Our results can be explained by the fact that the two populations have different origins and that the Sami population has remained smaller and more isolated than its neighbors.