摘要:

Abstract: Multiple sclerosis (MS) has, since the 1970s, been known to be associated with the HLA‐Dw2 and ‐DR2 specificities in Caucasian Europeans and North Americans. By the use of genomic typing techniques, the association has been specified to be with the DRwlS,DQw6,Dw2, i.e. the DRBI* 1501‐DQAI*0102‐DQBl*0602 haplotype. A significant DPw4 association in Scandinavian MS patients has been described in one report. However, this association has not been confirmed in several subsequent studies with patients from the same and other ethnic groups. During the last few years several reports, based on serological, RFLP and PCR‐SSO data, have suggested that the HLA class II‐associated MS susceptibility gene(s) may be more closely associated with theDQthan with theDRsubregion. The observations that theHLA‐DQBIgenes of MS patients share long stretches of sequence motifs and also carryDQA1alleles encoding glutamine at position 34 of the DQ α chain have received considerable attention. It has been suggested that the susceptibility to develop MS might be determined by the corresponding DQ α‐β heterodimers either encoded in cis or in trans. We have investigated these issues in a large group of Swedish MS patients (n= 179). We found that the associations with the suggestedDQBIsequences and position 34 of the DQ α chain were due to linkage disequilibrium and secondary to the association with the DRw15,DQw6,Dw2 haplotype (p<10‐9and pw2 haplotype. We have previously described immunogenetic differences between different clinical forms of MS. In the present study of a new group of MS patients compared with a new control panel, these differences were partly confirmed. The DRw17,DQw2 association in relapsing/remitting MS was affirmed. However, in patients with primarily chronic progressive MS a negative association with the DQw7 allele was not substantiated and a positive association with the DR4.DQw8 haplotype could ne

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02029.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract: We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes:HLA‐DRB, ‐DQA, ‐DQB, DPA, and ‐DPBin 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in PJRA when compared to normal controls:DRBI*08(DRw8) (35.2% vs 10.3%, RR = 4.6, p<10−3),DRB3*01/02/03(DRw52) (76.3% vs 48.1%, RR 3.5, p<10−3),DQAI*0401(41.0% vs 7.4%, RR = 7.9, p<10−3),DQAI*0501(55.6% vs 29.7%, RR = 3.0, p<10−2,DQBI*0301(DQw7) (46.2% vs 17.5%, RR = 4.0; p<10−2),DPA1*0201(44.2% vs 7.9%, RR = 8.7, p<10−5), and DPB1*02 (DPw2) (40.7% vs 7.1%, RR = 8.5, p<10−6). The frequency ofDRBI*IIwas not significantly increased. The frequencies of DNA fragments associated with the following HLA class II genes were decreased in PJRA although not statistically significantly so after‘correction’of p values:DRBI*04(14.8% vs 40.2%, RR = 0.27; p<10−3)DRB1*07(0% vs 25.9%, RR = 0.04, p<10−3),DRB4*0101(DRw53) (25.9% vs 53.6%, RR = 0.31, p<10−3),DQA1*0102(11.6% vs 36.0%, RR = 0.25, p<10−4) andDQA1*0201(2.6% vs 34.2%, RR = 0.05, p<10−2). Individuals who carried certain combinations of two of the risk factors seemed to have a further increased risk of developing PJRA compared to individuals carrying only one of the risk factors. The combinations of HLA class II genes primarily involved were:DRBI*08 and DQAI*0501, DRB1*08andDQB1*0301, DRB1*08 and DPA1*0201, DQA1*0401andDQB1*0301, DQA1*0401and DPA1*0201, DQA1*0501 andDPB1*0201, and DQA1*0501 andDPB1*02, although other combinations also gave odds ratios which were non‐significantly increased compared to the odds ratios of the individual genetic markers. The data suggest that HLA class II gene products coded by genes at different loci i

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02030.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract: We have determined alleles of HLA‐DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 loci in 91 unrelated healthy individuals from North China. Group‐specific PCR primers were employed for the analysis of subsets of DR1, DR2, DR4, DRw52, and DPB. With allele‐specific probes, 22 DRB1, 8 DQA1, 13 DQB1, and 12 DPB1 alleles were found in this panel. Allele frequencies showed that 25.3% of the subjects had DR7 and 26.4% had DR9, only 5.5% had DRB1*0301 (DRwl7). In the DR4 group, DRB1*0405 (Dw15, 8.8%) and 0406 (KT2, 9.9%) were the most prevalent alleles. DRB1*0404 (Dw14.1), 0407 (Dw13.2) and 0408 (Dw14.2) were absent and the other alleles of the DR4 group were rare. The most common DRw6 subset was DRB1*1401 (8.8%). DRB1*0802 and 0803 were present (2.2%, 6.6%), and DRB1*0801 was not found. Associations with DQA1 and DQB1 were generally similar to those found in other populations. DPB1*0501 was the most frequent (60.2%) allele at the DPB1 locus. Overall our study shows that the distribution of class I1 alleles in a population from Mainland China is quite different from other ethnic groups. The high frequency of the KT2 subset of DR4 (DRB1*0406) and of DPB1*0501 are the most striking features found. A new type of DR4 was determined in one subject. It was like DR4‐Dw15 (DRB 1*0405) but, according to our hybridization patterns, it encoded valine instead of glycine in position 86. It is now called DR

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02031.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02032.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02033.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02034.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02035.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02036.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1991.tb02037.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY