Association of the AChRalpha-subunit gene (CHRNA), DQA1*0101, and the DR3 haplotype in myasthenia gravis. Evidence for a three-gene disease model in a subgroup of patients.
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction having multigene control. HLA-linked loci and the HB*14 micro-satellite marker located within the CHRNA gene which encodes the muscular acetylcholine receptor (AChR) alpha-subunit, the target self-antigen, were previously associated with MG. Combined analysis of these loci revealed a significant increase of DQA1*0101 alleles in HB*14+ vs. HB*14- patients and of DQA1*0501 alleles in HB*14/DQA1*0101 patients. Importantly, the effect of DQA1*0101 was independent of allelically associated DQB1 and DRB1 genes. In contrast, the effect of DQA1*0501 could not be dissociated from that of DRB1*03 and DQB1*0201 on the extended DR3 haplotype. These results indicate that a combination of three genes, of which two are linked to HLA, contributes to disease susceptibility in a subgroup of MG patients.
Djabiri
F
F
INSERM Unit 25 and Institut Necker, Paris, France.
Caillat-Zucman
S
S
Gajdos
P
P
Jaïs
J P
JP
Gomez
L
L
Khalil
I
I
Charron
D
D
Bach
J F
JF
Garchon
H J
HJ
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics*
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D015803:HLA-DR3 Antigen; D011950:Receptors, Cholinergic