Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis.
With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [p<0.05, relative risk (RR)=9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p<0.005; RR=6.2), more frequent in females (p<0.005; RR=7.8) and most frequent in EOMG female patients (p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients. The combined effect of other intervening genes cannot be excluded.
Franciotta
D
D
Laboratory of Neuroimmunology, IRCCS, Foundation Neurological Institute C. Mondino, University of Pavia, via Palestro 3, 27100, Pavia, Italy. diego.franciotta@mondino.it
Cuccia
M
M
Dondi
E
E
Piccolo
G
G
Cosi
V
V
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D015934:Complement C4a / Q000235:genetics; D015935:Complement C4b / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005802:Genes, MHC Class II / Q000276:immunology*; D005819:Genetic Markers / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012727:Sex Characteristics
D005819:Genetic Markers; D008233:Lymphotoxin-alpha; D015934:Complement C4a; D015935:Complement C4b; C052380:endodeoxyribonuclease NcoI; D015252:Deoxyribonucleases, Type II Site-Specific; D011415:Complement Factor B