Extended major histocompatibility complex haplotypes in patients with gluten-sensitive enteropathy.

Abstract

We have studied major histocompatibility complex markers in randomly ascertained Caucasian patients with gluten-sensitive enteropathy and their families. The frequencies of extended haplotypes, defined as haplotypes of specific HLA-B, DR, BF, C2, C4A, and C4B allelic combinations, occurring more frequently than expected, were compared on patient chromosomes, on normal chromosomes from the study families, and on chromosomes from normal families. Over half of patient chromosomes consisted almost entirely of two extended haplotypes [HLA-B8, DR3, SCO1j and [HLA-B44, DR7, FC311 which, with nonextended HLA-DR7, accounted for the previously observed HLA markers of this disease: HLA-B8, DR3, and DR7. There was no increase in HLA-DR3 on nonextended haplotypes or in other extended haplotypes with HLA-DR3 or DR7. The distribution of homozygotes and heterozygotes for HLA-DR3 and DR7 was consistent with recessive inheritance of the major histocompatibility complex-linked susceptibility gene for gluten-sensitive enteropathy. On the other hand, by odds ratio analysis and from the sum of DR3 and DR7 homozygotes compared with DR3/ DR7 heterozygotes, there was an increase in heterozygotes and a decrease in homozygotes suggesting the presence of modifying phenomena.

An extended HLA-D region haplotype associated with celiac disease.

“…Thus, the strong linkage disequilibrium normally observed between the HLA-DR and -DQ subregions would be extended, on this haplotype, throughout the entire HLA-D region. The celiac disease-associated HLA-DR3 haplotype was recently shown to be extended telomerically from the subregion encoding HLA-DR3 through the genes encoding the complotype SC01 to the HLA-B8 locus (26). Similarly, our findings indicate that this HLA-DR3, -DQw2 haplotype may have an unusual degree of linkage disequilibrium, extending centromerically from the HLA-DR subregion to the HLA-DP subregion.…”

O sistema complemento nas doenças: genética e patogenia

“…Destacam-se, entre esses, os achados de Alper, et al (57) , demonstrando aumento na freqüência dos haplótipos [HLA-B8, DR3, BF*S, C2*C, C4A*Q0, C4B*1] e [HLA-B44, DR7, BF*F, C2*C, C4A*3, C4B*1] em pacientes celíacos caucasóides, bem como os resultados obtidos por Mannion, et al (58) com aumento do haplótipo [HLA-B8, DR3, DQW2, BF*S, C4A*Q0 e C4B*1] em pacientes irlandeses. Estudos com pacientes italianos caracterizaram aumento significativo na freqüência do alelo BF*F1, em relação a população normal, e uma associação de BF*F1 com Dw3 e de BF*F com Dw7 (59) .…”

Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients

“…In North European populations, the DQA1*05 and DQB1*02 alleles are frequently present on the extended HLA-B8-DR3-DQ2 haplotype. 6,9 This haplotype has also been shown to be associated with other autoimmune disorders, including type I diabetes mellitus, systemic lupus erythematosus, Graves' disease, Hashimoto's disease and myasthenia gravis, suggesting that the genes on this haplotype are involved in autoimmunity in general (for a review, see Candore et al 10 ). In coeliac disease, it was shown that different DQ2 genotypes account for different disease risks.…”