Association of TAP and HLA-DM genes with psoriasis in Koreans.
To investigate the possible involvement of antigen-processing genes in the pathogenesis of psoriasis, we analyzed the polymorphisms of the TAP1, TAP2, LMP2, LMP7, DMA, and DMB genes in 98 Korean psoriasis patients and compared them with 184 healthy controls. The frequencies of TAP2*B/B [relative risk (RR)=3.6, p<0.0002] and TAP2*B (RR=1.7, p<0.05) were significantly increased, but TAP1*B (RR=0.3, p<0.002) and TAP2*A (RR=0.6, p<0.03) were significantly decreased, in the patients compared to the controls. We performed further analysis on the TAP1 and TAP2 single nucleotide polymorphisms and found significant differences between the patients and controls in TAP1 single nucleotide polymorphism at position 637 and in TAP2 at 665. In HLA-DM, DMA*0102 (RR=2.5, p<0.0003) was significantly increased, but DMA*0101/0101 (RR=0.4, p<0.0004) and DMB*0103/0103 (RR= 0.3, p<0.005) were significantly decreased in the patients compared to the controls. The TAP and HLA-DM alleles were also analyzed according to the age of onset of psoriasis in the patients (types I and II). It was found that the HLA-DM alleles showed a greater association in type I than type II patients. An analysis of the linkage disequilibrium and stratification also indicated that the alleles of TAP and HLA-DM might be independently associated with HLA-Cw*0602 in psoriasis patients. The stratification analysis between DMA*0101/0101 and DMB*0103/0103 showed that a certain factor, controlled by a gene located between DMA and DMB, might provide strong protection against psoriasis, independently of Cw*0602, in our Korean population. In conclusion, our data suggest that the TAP and HLA-DM alleles could lead to genetic susceptibility toward psoriasis in Koreans.
Pyo
Chul-Woo
CW
Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Hur
Seong-Suk
SS
Kim
Yang-Kyum
YK
Kim
Tae-Yoon
TY
Kim
Tai-Gyu
TG
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003546:Cysteine Endopeptidases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics; D006681:HLA-D Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes; D011110:Polymorphism, Genetic; D046988:Proteasome Endopeptidase Complex; D011565:Psoriasis / Q000235:genetics*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015236:HLA-C Antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex