HLA restriction fragment length polymorphisms associated with insulin-dependent diabetes mellitus and the seronegative spondyloarthropathies

Acton, Ronald T.; Hodge, Thomas; McDaniel, D. Olga; Reveille, John D.; M, Napier-Littrell; Barger, Bruce O.

doi:10.1007/bf01119893

Cited by 5 publications

(2 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OOlOl), the proband carries the 9.2-kb RFLP and expresses the B27 phenotype, the 9.2-kb RFLP clearly segregates independently of the B27 phenotype. We have also observed that the segregation of the 9.2-kb Pvu I1 fragment in control families may be indepenxnt of the B27 phenotype (27). The preliminary data from family studies thus suggest that the 9.2-kb RFLP represents a disease susceptibility marker which is distinct from B27.…”

Section: Mcdaniel Et Almentioning

confidence: 61%

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

McDaniel

Acton

Barger

et al. 1987

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

We analyzed DNA restriction fragment length polymorphism (RFLP) in 53 white ankylosing spondylitis (AS) patients and 92 healthy controls, utilizing a full-length HLA-B7 complementary DNA probe. A 9.2-kilobase (kb) Pvu I1 fragment was found to be significantly increasexn frequency in B27 positive AS patients compared with the B27 positive control group (P = 0.00085, relative risk = 7.2). The presence of both B27 and the 9.2-kb RFLP in an individual conferred a relative risk for AS of 297, compared with a relative risk of 119 in those who had B27 alone. The 9.2-kb RFLP appears to be a marker for AS which, with HLA-B27, contributes further to susceptibility to the disease. Our The seronegative spondylarthropathies, including ankylosing spondylitis (AS), Reiter's syndrome, psoriatic arthritis/spondylitis, and the arthritidspondylitis of inflammatory bowel disease, constitute a heterogeneous group of disorders characterized by axial and/or peripheral arthritis, overlapping clinical features, a tendency toward familial aggregation, and the absence of rheumatoid factor or subcutaneous nodules (1). Although the association of AS and other seronegative spondylarthropathies with HLA-B27 is well documented (2,3), the precise role of B27 in the genetic susceptibility to AS is yet to be established. There is a marked discrepancy between the frequency of this antigen in the white population (6.8%) and the prevalence of AS (0.2%), which raises the possibility that a unique subtype of B27 or a linked gene might be more disease-specific. As many as 6 B27 subtypes have been identified by a combination of approaches, including monoclonal antibody studies (4), cytotoxic T lymphocyte studies (5,6), a restriction typing assay (7), high performance liquid chromatography peptide mapping @), and amino acid and nucleotide sequencing (9,lO). Different B27 variants have exhibited higher or lower prevalence according to ethnic group (1 1,12).The availability of complementary DNA (cDNA) probes specific for the class I major histocompatibility complex (MHC) region genes permits further definition of these genes at the DNA level. A useful approach in this regard has been the technique of restriction fragment length polymorphism (RFLP)

show abstract

Section: Mcdaniel Et Almentioning

confidence: 61%

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

McDaniel

Acton

Barger

et al. 1987

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, it has been suggested that the DR3 and DR4 types are associated with different traits of the disease, suggestive of a genetic heterogeneity [35,36,49]. Molecular analyses ofthe HLA region on chromosome 6 have revealed that individuals with or without IDDM but with identical HLA-DR specificities differ at the H L A-DQ locus as detected by restriction fragment length polymorphism (RFLP) [ 1,9,14,15,22,24,38,41,44,45], locus-specific oligonucleotide probes [25,43], two-dimensional gel electrophoretic analysis [2,42], or direct sequencing using the polymerase chain reaction [53], Taken together, these analyses have indicated that HLA-DQ is more strongly associated with IDDM, particularly in DR4-positive [38 41, 43, 53] patients. In these patients, HLA-DQw7 (HLA-DQw3,l or aspartic acid in position 57, Asp-57) is significantly less frequent than the DR4-linked, HLA-DQw8 ailele (HLA-DQw3,2, often non-Asp in position 57) [2,42,43,53], As previously reported, we cloned and sequenced a BamH 1 3,7kilobase (kb) fragment and thereby mapped this fragment to the DQ locus as a DQw7-associated polymorphism [38], A probe derived from part of the first intervening sequence and part of the second coding sequence (IVSl) showed BamH I fragments of 12 kb and/or 4 kb among 98% of IDDM patients younger than 20 years of age at onset compared with 63% of the controls [38], There is evidence to suggest that the BamH I 12kb fragment is associated with DQw8 and the 4kb fragment with DQw2 [41], however the frequency with which those two fragments were detected among controls did not correspond to the frequencies of currently known DQ specificities.…”

mentioning

confidence: 99%

HLA Heterozygosity in Insulin‐Dependent Diabetes is Most Frequent at the DQ Locus

et al. 1990

View full text Add to dashboard Cite

Restriction fragment length polymorphism using an HLA-DQ beta-chain genomic probe showed that 63 children with insulin-dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA-DR3 and/or 4 and 75% (47/63) for HLA-B8 and/or 15. The 36 (56%) DR3-positive children were all 4-kb-positive; however, a total of 44 (70%) children were 4-kb-positive (P less than 0.02). The 55 (87%) DR4-positive children were all 12-kb-positive, but a total of 56 (89%) were 12-kb-positive (NS). The heterozygosity at the HLA region increased from 11/63 (18%) for HLA-B8/15 to 29/63 (46%) for HLA-DR3/4 (P less than 0.0004) and to 37/63 (59%) for the HLA-DQ 4 kb/12 kb fragments (P less than 0.02). The test of an equal probability of a positive result under the adjacent pair of tests indicates that the increased risk of developing IDDM in association with HLA-DQ is to a great extent due to heterozygosity at this locus. There were no differences between the 4 kb/12 kb and the DR3/4-positive IDDM children with respect to fasting or meal-stimulated C peptide, insulin requirement, or levels of insulin antibodies formed during the first 12 months of insulin therapy. Our results support the hypothesis that HLA-DQ is closely associated with an increased risk of childhood IDDM, and when typed for at this locus parameters of the clinical course were homogeneous, suggesting that factors other than HLA-DQ may determine previously observed differences between IDDM children in clinical or functional parameters.

show abstract

Islet‐specific immune mechanisms

Lernmark

Shen

Bækkeskov

et al. 1987

Diabetes Metab. Rev.

View full text Add to dashboard Cite

HLA restriction fragment length polymorphisms associated with insulin-dependent diabetes mellitus and the seronegative spondyloarthropathies

Cited by 5 publications

References 42 publications

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

Association of a 9.2‐kilobase pvu ii class i major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis

HLA Heterozygosity in Insulin‐Dependent Diabetes is Most Frequent at the DQ Locus

Islet‐specific immune mechanisms

Contact Info

Product

Resources

About