Extended haplotypes of chromosome 6 in adult rheumatoid arthritis

Raum, Donald; Awdeh, Zuheir L.; Glass, David N.; Khan, Muhammad Asim; Coblyn, Jonathan S.; Weinblatt, Michael E.; Holdsworth, Donald; Strong, Louise C.; Rossen, Roger D.; Brewer, Earl J.; Yunis, Edmond J.; Alper, Chester A.

doi:10.1002/art.1780270506

Cited by 27 publications

(11 citation statements)

References 24 publications

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“…This method of establishing control gene frequency and control haplotype frequencies using the proband's family has been compared with a method in which haplotype frequencies are derived from families without an affected member. Very comparable results have been obtained between the 2 methods (14). Control gene frequencies for HLA-DR were also compared with HLA-DR data for North American whites from the 8th International Histocompatibility Workshop ( 1 5 ) , and no significant differences were found by the application of chi-square statistics (12).…”

Section: Arthritis and Rheumatism Vol 28 No 2 (February 1985)mentioning

confidence: 82%

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis

Miller

Aaron

Jackson

et al. 1985

Arthritis & Rheumatism

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The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (x2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.

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Section: Arthritis and Rheumatism Vol 28 No 2 (February 1985)mentioning

confidence: 82%

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis

Miller

Aaron

Jackson

et al. 1985

Arthritis & Rheumatism

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“…However, we want to point out that penetrance is not complete, since there are several family members who have this superhaplotype, but do not have RA. The DR4-containing superhaplotypes have been studied in detail by many groups of investigators (18)(19)(20). One of the superhaplotypes studied is B w62 (split of B 1 S);C4A3 ; C4B2.9;Bf S;DR4, and another is Bw62;C4A3;C4Bl;BfS;DR4.…”

Section: Discussionmentioning

confidence: 99%

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

Wallin

Carlsson

Ströum

et al. 1988

Arthritis & Rheumatism

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Forty-three patients with seropositive, erosive rheumatoid arthritis (RA) and 24 members of 5 RA multicase families were studied for HLA class I1 gene polymorphism, using restriction fragment analysis with complementary DNA probes for DRP and DQP chains. This method generates HLA-DR-DQ haplotypes that are highly correlated with HLA-DR serology. Thirtyfive of the 43 RA patients (81%) were positive for one or for both of the DR4-associated DR-DQ haplotypes, 4.1 and 4.2. Among these patients, the 4.1 haplotype was found significantly more often than in DR4 + controls (P < 0.01). The haplotype segment C3;B15;DR4 was present in all RA patients in 4 of the 5 families, and included the DR-DQ4.1 haplotype.The etiology of rheumatoid arthritis (RA) is still unknown. However, for a long time, a constitutional basis for susceptibility to the disease has been implicated, and this is strongly supported by the finding of Address reprint requests to Johan Wallin, Center for Biotechnology, F82, Huddinge Hospital, S-141 86 Huddinge, Sweden.Submitted for publication November 26, 1986; accepted in revised form May 27, 1987. an association between RA and HLA-Dw4 (1). This specificity is defined using homozygous typing cells. When serologic means of studying class I1 mixed lymphocyte culture (MLC) antigens were introduced, findings clearly indicated that RA was closely associated with HLA-DR4. More recently, additional class 11 loci have been defined using both serologic and cellular typing techniques. Three of these loci contained genes encoding polymorphic products and are now referred to as DP, DQ, and DR.DR antigens have been well characterized using serologic methods, and so far, 12 distinct allelic products have been defined. The DQ locus is closely linked to DR; the DQ alleles exist in strong linkage disequilibrium with particular DR alleles. Serologic typing has only revealed 3 distinct DQ allotypes: wl, w2, and w3. Linkage disequilibrium between DR and DQ is exemplified by the fact that almost all DR4 + individuals are also DQw3 + .New methods have recently been used to study the association between HLA and diseases. Complementary DNA (cDNA) probes have been used to genotype patients for class I1 alleles. A method based on restriction fragment length polymorphism (RFLP) has been developed (2) that, together with recent findings (3), gives a solid basis for the assignment of genetically defined DR-DQ haplotypes, which correlate extremely well with the serologic DR specificities. DRP-specific RFLP gives a resolution similar to that which can be observed when serologic reagents are used. However, genotyping shows a higher degree of polymorphism for the DQ locus than was determined from earlier serologic studies. In 1985, Bohme et a1 (2) defined 7 distinct DQP subtypes. The association between HLA class I1 alleles and insulin-dependent

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Section: Introductionmentioning

confidence: 99%

“…Thus, in celiac disease, an increase in HLA-DQw2 results from increases in the frequency of SCO1, DR3, DQw2] and FC31, DR7, DQw2] (14). Similarly, in type 1 diabetes mellitus and rheumatoid arthritis, the increased frequencies of individual alleles are associated with increases in specific extended haplotypes that bear them (15,16).To determine if the increased frequency of DR4 in OCP was associated with an increase in a specific DR4-bearing extended haplotype and, in particular, if the DR4 was DQw7-or DQw8-associated, patients with OCP and their families were studied for HLA-A, -B, -DR, and -DQ, the serum complement proteins BF, C2, C4A, and C4B, and restriction fragment length polymorphisms (RFLPs) in DRB, DQB, and DPB. Our findings suggest that HLA-DQB1*0301, rather than an extended MHC' haplotype bearing this allele, is a marker for susceptibility to OCP.…”

mentioning

confidence: 99%

Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid.

Ahmed

Maleki

Zaltas

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and H and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB1*0301). The frequency of DQB1*0301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P < 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB1*0301 among the patients was consistent with dominant but not recessive inheritance of DQB1*0301 or a gene, probably a class H allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP.Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects multiple mucous membranes (1-3). If not treated or treated inappropriately when it affects the eyes, it can cause blindness. The pathologic processes of chronic cicatrizing conjunctivitis and progressive conjunctival subepithelial fibrosis that characterize this disease result in severe xerosis of the eye and ocular keratinization.The deposition of immunoglobulins and complement components at the basement membrane zone (BMZ) (4-6) of the involved mucosa appears to be pathogenetic. Inflammatory mediators in the preocular tear film contribute to the final pathologic changes (3). Circulating antibodies to BMZ have been demonstrated in the serum of OCP patients, using skin and buccal mucosa as substrate (7,8).There have only been a few studies of HLA antigen frequencies in patients with OCP. The initial reports (6, 9) of an increased frequency of HLA-B12 (HLA-B44 or B45) were not confirmed in later studies (3, 10). Recently (11), we reported an increase in the frequency of the HLA-DR4 allele in OCP patients. In patients with pemphigus vulgaris, the increased frequency of DR4 is ascribable to the increased frequency oftwo haplotypes, SC21, DR4, DQw8] and SC31, DR4, DQw8], particularly in Ashkenazi Jewish patients (12). The first of these is a known extended haplotype (13) (a haplotype with fixed DNA over at least the HLA-B/DR interval) in this ethnic group. In a number of major histocompatibility complex (MHC) alleleassociated diseases, the increase in specific alleles is secondary to the increase in one or more extended haplotypes that carry suscepti...

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Extended haplotypes of chromosome 6 in adult rheumatoid arthritis

Cited by 27 publications

References 24 publications

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid.

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