title: Absence of primary association between DM gene polymorphism and insulin-dependent diabetes mellitus or celiac disease.
abstract: The DMA and DMB genes encode class II-like heterodimetric molecules located in a specialized endocytic compartment, where they facilitate efficient loading of antigenic peptides on HLA class II molecules. Both genes are located within the MHC class II region and present a limited allelic polymorphism. Here we report the distribution of DM alleles in a group of 75 IDDM patients, 72 CD patients, and 162 random controls. We found a pronounced decreased frequency of DMA*0102 in both patient groups relative to controls. This difference was, however, mainly secondary to a strong negative linkage disequilibrium (LD) between this allele and the IDDM and CD-associated DRB1*03 allele. The DMB phenotype frequencies were similar in CD patients and controls. By contrast, we observed a decreased frequency of DMB*0101 and an increased frequency of DMB*0102 and DMB*0104 in IDDM patients. These differences disappeared when matching individuals for DRB1*03 or DRB1*04 alleles, which was in accordance with strong negative LD between DMB*0101 and DRB1*04 or DQB1*0302 alleles, and positive LD between DMB*0104 and DQB1*0201. Our data suggest that the apparent associations of IDDM or CD with given DM alleles are mostly secondary to primary associations with alleles at the DRB and DQB loci.
authors.affiliation: INSERM U25, Hopital Necker, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Djilali-Saiah
authors.forename: V
authors.initials: V
authors.lastname: Benini
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: J
authors.initials: J
authors.lastname: Timsit
authors.forename: R
authors.initials: R
authors.lastname: Assan
authors.forename: C
authors.initials: C
authors.lastname: Boitard
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: S
authors.initials: S
authors.lastname: Caillat-Zucman
mesh_terms: D002446:Celiac Disease / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D011110:Polymorphism, Genetic / Q000276:immunology*
chemical_list: C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II