Complex genetic predisposition in adult and juvenile rheumatoid arthritis.
BACKGROUND
Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are complex multifactorial diseases caused by environmental influences and an unknown number of predisposing genes. The present study was undertaken in order to investigate association of polymorphisms in candidate genes with RA and JRA in German subjects.


RESULTS
Up to 200 unrelated German RA and JRA patients each and 300-400 healthy controls have been genotyped for HLA-DRB1, TNFa, TNFA -238a/g, TNFA -308a/g, TNFA -857c/t, TNFR1 -609g/t, TNFR1 P12P, TNFR2 del 15bp, IKBL -332a/g, IKBL -132t/a, IKBL C224R, CTLA4 -318c/t, CTLA4 T17A, PTPRC P57P, MIF -173g/c, the MIF and IFNG microsatellites as well as for D17S795, D17S807, D17S1821 by polyacrylamide gel electrophoresis, single-strand conformation polymorphism analysis, restriction fragment length polymorphism analysis or allele specific hybridization. None of the investigated genetic markers is associated with both, RA and JRA, but there are some statistically significant differences between patients and controls that have to be discussed sensibly.


CONCLUSIONS
The difficulty in investigating the genetics of complex disorders like RA and JRA may arise from genetic heterogeneity in the clinically defined disease cohorts (and generally limited power of such studies). In addition, several to many genes appear to be involved in the genetic predisposition, each of which exerting only small effects. The number of investigated patients has to be increased to establish the possibility of subdivison of the patients according their clinical symptoms, severity of disease, HLA status and other genetic characteristics.
Miterski
Bianca
B
Department of Human Genetics, Ruhr-University Bochum, Germany. miterski@eurogen.de
Drynda
Susanne
S
Böschow
Gundula
G
Klein
Wolfram
W
Oppermann
Joachim
J
Kekow
Jörn
J
Epplen
Jörg Thomas
JT
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D000943:Antigens, Differentiation / Q000235:genetics; D001171:Arthritis, Juvenile / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D060908:CTLA-4 Antigen; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C120111:NFKBIL1 protein, human; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA; D017493:Leukocyte Common Antigens