Genetic markers of immunoglobulins and diabetes mellitus in the multiracial population of New Caledonia. The CALDIA Study Group.

GM and KM immunoglobulin allotypes, which are the markers, respectively, of the constant parts of the heavy and the light chains of the IgG1, IgG2 and IgG3 subclasses, have been analysed in diabetic mellitus patients and controls living in New Caledonia. We tested 40 Europeans, 256 Melanesians and 44 Polynesians, as well as their 340 matched controls, in order to search for a genetic susceptibility at those polymorphic loci. All the subjects were tested for G1M (1, 2, 3, 17), G2M (23), G3M (5, 6, 10, 11, 13, 14, 15, 16, 21, 24, 28) and KM (1) by the classical hemagglutination method. The frequencies of GM haplotypes and KM alleles have been estimated by a maximum likelihood method. The results are in favour of no influence of the GM and KM loci. The prevalence of diabetes mellitus varies in the populations of New Caledonia: Polynesians are at much higher risk than Melanesians or Europeans. The GM haplotype distribution differs among ethnic groups; so they provide a useful marker to measure genetic admixture. The higher prevalence of diabetes observed among New Caledonians of European origin compared to the prevalence in Europe may be explained by genetic admixture with neighbouring Pacific populations, notably Polynesians (Asian haplotypes are present at a frequency of 9.4%). So, the genetic admixture should be measured in any genetic epidemiological study.

Genetic diversity in northern Spain (Basque Country and Cantabria): GM and KM variation related to demographic histories.

Genetic diversity in Northern Spain (SW Europe) was assessed through the analysis of the GM and KM immunoglobulin markers in 505 individuals using a set of 17 allotypes, including the G2M(23) allotype which has been infrequently used before now. The individuals were representative of three anthropologically well-defined populations belonging to two geographically and archaeologically distinct areas in the Basque Country (Guipúzcoa and Alava provinces) and to the mountainous region of Montes de Pas in the province of Cantabria. Gene frequency distributions indicated a high genetic divergence between Montes de Pas and the Basque Country, and a relative degree of heterogeneity between the two Basque regions. The genetic differentiation of Montes de Pas, which is consistent with previous classical polymorphism analyses, suggests a considerable genetic variation range within the Iberian Peninsula, possibly higher than that often polarised around the Basque versus non-Basque variation. Analyses of genetic structure show that the major differentiation of Montes de Pas could be related to the historically documented mixed origin of this population. The moderate genetic distances between regions in the Spanish Basque Country could be explained by differential systematic pressures acting through a stronger gene flow in the South than in the more isolated Northern areas. The comparisons with neighbouring populations from the French Pyrenees suggest that the present genetic variation revealed by lg polymorphisms in SW Europe can be related to historical demographic processes including gene flow and/or low population sizes.

GM and KM immunoglobulin allotypes in a Spanish Pyrenean population: Val d'Aran.

Four hundred and thirteen unrelated individuals (202 autochthonous and 211 non-autochthonous) of Val d'Aran (Catalan Pyrenees) have been analysed for the GM and KM immunoglobulin genetic system using the inhibition haemagglutination method. This population was defined by eight GM haplotypes (GM*3 23 5*, GM*3 5*, GM*1,17 21,28, GM*1,2,17 21,28, GM*1,17 5*, GM*1,17 5,6,11,24, GM*1,17 10,11,13,15 and GM*1,17 10,11,13,15,16) inferred from the 17 observed phenotypes. The Val d'Aran population frequencies conform to Hardy-Weinberg expectations. The frequencies of phenotypes and haplotypes show a definite homogeneity between the autochthonous and non-autochthonous people of Val d'Aran and 11 other Pyrenean populations (Mauléon, Macaye, St. Jean Pied de Port, Vallée de L'Ouzom, Gavarnie, Barèges, Luz St. Sauveur, Esparros, Camurac, Capcir and Pays de Sault) that have already been studied for the same allotypes. A factorial correspondence analysis was performed for the 12 autochthonous Pyrenean populations, showing a high frequency of the GM*3 23 5* haplotype in the three Pyrenean regions (Western, Central and Eastern), while the GM*1,17 21,28 haplotype is mainly found in the Central region, GM*3 5* in the Eastern and Western zones, and the GM*1,2,17 21,28 is mainly present in the Central and Eastern populations. The results show a relative regional homogeneity, so there is no evidence of a frequency gradient in the Pyrenean populations for the GM and KM genetic systems. It may, however, be noticed that the Central Pyrenean populations form a group, with one population (Vallée de l'Ouzom) isolated from the rest, probably because of its particular model of inheritance by which the heritage is passed to the first born without sex consideration. It has been possible to point out some differences in the genetic structure of the autochthonous and non-autochthonous Val d'Aran population and to place the autochthonous Aranese group among its Pyrenean neighbours.

Human genetic diversity (immunoglobulin GM allotypes), linguistic data, and migrations of Amerindian tribes.

GM haplotype frequencies were examined in 49 Amerindian tribes (from North, Central, and South America) to investigate the congruence of genetic variation with that observed in language and geography. We used two approaches: (1) the mobile site method, which allows a two-dimensional representation of genetic variation where the distances between reference points (i.e., the locations of the populations in the geographic map after displacements) are close to the genetic distances, and (2) a multivariate analysis (factorial correspondence analysis), which permits a visual interpretation of the geographic distribution of GM haplotypes on a map, completed by a cluster analysis. The results show a strong gradient from the Bering Strait to South America. The Eskimo and Na-Dene are genetically different from all other Amerindians, reflecting their more recent migrations. The orientation of most trajectories of the tribes from Central and South America can be interpreted as earlier migrations along the Pacific and Atlantic coasts. We conclude that geographic and linguistic factors played a part in the genetic diversity of Amerindian tribes.

Gm and Km allotypes in Wayampi, Wayana and Emerillon Indians from French Guiana.

We have studied 506 Amerindians from three French Guiana groups: 194 Wayampi, living in Trois-Sauts, and 100 in the Camopi area; 47 Emerillon also living in the Camopi area and 165 Wayana on the Litani and Maroni rivers. All samples were tested for G1m(1,2,3,17), G3m(5,6,10,11,13,14,15,16,21,24,28) and Km(1) by the classical method of hemaglutination inhibition. The phenotype and haplotype distributions are presented and have been subjected to factorial correspondence analysis. Two Gm haplotypes are common: Gm1,17;21,28, and Gm1,2,17;21,28, but with an important variation in frequency. A rare haplotype, probably the result of a genetic anomaly: Gm1,17;21R,28, is frequent in the Emerillon (17%). These populations show no evidence of Black or Caucasian admixtures.

Gm and Km allotypes in autoimmune diseases.

The associations or linkages between the polymorphisms of the Gm and Km immunoglobulin allotypes and the susceptibility to autoimmune diseases, including diseases with immuno-pathological pathogenesis are reported in this review. These diseases include multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, Crohn's disease, coeliac disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. Immunoglobulin allotypes are described as well as the statistical methods used to analyse the data.