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Results for “HLA polymorphism”

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At least 1,009 records · Page 56Linked to original sources
PubMed2000

MICA gene triplet repeat polymorphism in patients with HLA-B27 positive and negative ankylosing spondylitis from Sardinia.

OBJECTIVE: We investigated the distribution of MICA triplet repeat polymorphism in a random population and in patients with seronegative spondyloarthritis from Sardinia compared to continental Italy. METHODS: We analyzed the distribution of MICA triplet repeat polymorphism in HLA-B*2709 [not associated with ankylosing spondylitis (AS)] and B*2705 (associated with AS) haplotypes, to verify whether the strong association of MICA-A4 with HLA-B27 reported in other populations is maintained in Sardinia, and compared the distribution of MICA-A alleles in HLA-B27 negative versus HLA-B27+ patients with AS. RESULTS: We found that the frequency of MICA-A4 triplet repeat allele in a random Sardinia population is higher (53.2%) than in other Caucasian populations (around 20%); this allele is strongly associated with both HLA-B*2709 and B*2705. No significant difference between HLA-B27+ patients with AS and healthy controls was found: the MICA-A4 allele was present in more than 90% of subjects. MICA-A4 was found in 16 out of 20 HLA-B27 negative Sardinian patients with AS, with a frequency (80%) more similar to that of the HLA-B27+ group of patients than that of controls. CONCLUSION: The high frequency of MICA-A4 allele in HLA-B27 negative patients with AS from Sardinia, suggests the presence within the HLA region of a susceptibility factor other and certainly weaker than B27. This factor is likely to be more easily found by analyzing genetically homogeneous populations like the Sardinian, characterized by a small number of very frequent haplotypes.

HLA-B27 Antigen↗
PubMed1998

TNFB gene polymorphism in insulin-dependent diabetes mellitus: association with HLA-DR alleles.

A polymorphism of the TNF-beta gene can be detected by restriction digestion of a PCR product with NcoI. In this study we look at the risk associated with this polymorphism in a study of 69 insulin-dependent diabetes patients and 119 healthy controls. The risk was further characterized by comparison to the HLA type of the individual, since the TNF polymorphism is in linkage disequilibrium with HLA genes.

Alleles↗
PubMed2001

Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population.

The aim of this study was to examine whether the association of psoriatic arthritis (PsA) with human leukocyte antigen (HLA) class I genes is secondary to linkage disequilibrium with a nearby gene. We examined a sample of the Jewish population to investigate whether HLA-B/C and DR polymorphism is associated with susceptibility, or whether other closely related class I loci, such as the major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor (TNF), might play a role in disease development. Comparisons of different populations with different HLA profiles would be of value in identifying the candidate genes involved in PSA. Fifty-two patients with PsA and 73 random matched controls from a Jewish population were selected and DNA typed by polymerase chain reaction-single-strand oligonucleotide probe (PCR-SSOP) (HLA-C), PCR sequence-specific primers (PCR-SSP) (HLA-B, -DR), radioactive PCR (MICA-TM polymorphism in the transmembrane region), and PCR-RFLP (TNF). Some findings can be concluded from the study: (1) the frequency of HLA-B*5701, B*3801, B*39, B*27, Cw*0602, Cw*07, DRB1*0402, and DRB1*0701 were not found to be significantly increased in PsA; (2) no significant differences of TNFalpha promoter alleles at positions -308 and -238 were found between PsA and healthy controls; (3) the trinucleotide repeat polymorphism MICA-A9 was present at a higher frequency in PsA patients, (p(c) < 0.009, RR = 3.34, EF = 0.39); and (4) MICA-A9 polymorphism was found in linkage disequilibrium with HLA-B alleles (B*5701, B*3801) described to be associated with PsA in Caucasians. These results suggest that the MICA gene or other nearby gene(s) may be involved in the development of PsA, and it would thus appear that psoriasis vulgaris (PsV) and PsA are associated with different MHC susceptibility genes.

Adult↗
PubMed1991

HLA-DR: serology versus restriction fragment length polymorphism.

The results of the serological typing and the patterns of restriction fragment length polymorphisms for the detection of HLA-DR gene products are compared. The data shown demonstrate that the use of DNA typing gives a clearer definition of the HLA-DR antigens and that the HLA-DR polymorphism is greater than detected by serology.

DNA Probes↗
PubMed2002

Angiotensin-converting enzyme gene polymorphism in relation to HLA-DR in sarcoidosis.

OBJECTIVES: To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene associates with HLA-DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA-DR alleles, such as a good (DR17) or poor (DR14 or 15) prognosis. DESIGN, SETTINGS AND SUBJECTS: Polymerase chain reaction (PCR) was used for analysing an I/D polymorphism in the gene coding for ACE in 138 subjects; 65 controls and 73 sarcoidosis patients, and for HLA-DR genotyping 67 patients. Serum ACE level (S-ACE) was measured in all controls and 72 patients. Sixty-one patients were classified as chronic or nonchronic after 2 years follow-up. All patients were recruited and followed at our outpatient clinic. RESULTS: No significant differences in ACE alleles or genotypes were seen between controls and patients or between patients positive and negative for DR17 or DR14/15. The ACE genotype did not differ between nonchronic and chronic patients. The ACE genotype tended to influence the S-ACE in patients, whilst in controls S-ACE significantly differed between the ACE genotypes. CONCLUSION: This study does not support an association between ACE genotype and sarcoidosis or disease outcome. However, because significantly (P < 0.001) more DR17 positive (17 of 19) than DR14/15 positive (seven of 26) patients were classified as nonchronic, these results instead strengthen the prognostic importance of HLA-DR alleles in Scandinavian sarcoidosis patients.

Adult↗
PubMed1998

[The polymorphic study of HLA-DRB1 gene in Chinese Liaoning Han with PCR-sequence specific primers].

8 allele and group specificity at HLA-DRB1 locus were genotyped in 159 unrelated individuals of Liaoning Han, with polymerase chain reaction-sequence specific primers. The range of gene frequencies was from 0.02201-0.23899. Heterozagosity was 83%. 33 out of 36 theoretical genotypes were identified and the result conformed to Hardy-Weinberg equilibrium law. The present method can be used not only in paternity test, individual identification, but also in clinic graft matching between donor and recipient as well as the study of HLA.

Alleles↗
PubMed1998

[Polymorphism of the HLA-DRB1 04 gene in inhabitants of Tuva].

Data on the HLA-DRB1 04 gene typing among Tuvinians from Kyzyl are presented. Experiments were conducted by using the hybridization of allele-specific oligonucleotides with the amplified fragments of high molecular-weight DNA and reverse hybridization. The HLA-DRB1 0401 allele was most frequent among DR4-positive individuals. The HLA-DRB1 0405 and HLA-DRB1 0403 alleles were found at somewhat lower frequencies. In one individual, the rare HLA-DRB1 0410 subtype differing from HLA-DRB1 0405 subtype by the substitution of glycine for valine in codon 86 was detected.

Adolescent↗
PubMed2005

High-resolution genotyping of HLA-DQA1 in the GoKinD study and identification of novel alleles HLA-DQA1*040102, HLA-DQA1*0402 and HLA-DQA1*0404.

In order to achieve high-resolution HLA-DQA1 genotyping, it is necessary to identify polymorphisms in exons 1, 2 and 3. We present a high-resolution sequence-based typing (SBT) strategy for genotyping exons 1, 2 and 3 of the polymorphic HLA-DQA1 locus. This method is an improvement upon previously presented methods, because it utilizes the minimum number of SSP-PCR assays to obtain clear DNA sequence in both the forward and reverse directions of all three exons. All known HLA-DQA1 alleles are resolved with the exception of HLA-DQA1*010101 and HLA-DQA1*010102 for which the distinguishing polymorphism is located in exon 4 and does not result in an amino acid change. This method has enabled our laboratory to identify three new HLA-DQA1 alleles - HLA-DQA1*040102, HLA- DQA1*0402 and HLA-DQA1*0404 - in the Genetics of Kidneys in Diabetes (GoKinD) study population. Additionally, we present single-allele amplification methods, which identify the coding sequences of HLA-DQA1 exons 1, 2, 3, intron 2 and 300 bp of the HLA-DQA1 promoter (QAP). This study, also describes the QAP for most of the known HLA-DQA1 alleles, three HLA-DQA2 promoter sequences and the intron 2 sequences for HLA-DQA1*040101, HLA-DQA1*040102, HLA-DQA1*0402 and HLA-DQA1*0404.

Alleles↗
PubMed1993

Apparent genetic difference between hypothyroid patients with blocking-type thyrotropin receptor antibody and those without, as shown by restriction fragment length polymorphism analyses of HLA-DP loci.

HLA types in Japanese patients with primary hypothyroidism were analyzed to see whether those with blocking-type TSH receptor antibody (TSH-R BAb M) differed genetically from those with idiopathic myxedema (IM). HLA typings of -A, -B, -C, -DR, and -DQ (73 antigens) were performed serologically, and those of -D and -DP (29 antigens) were analyzed by the restriction fragment length polymorphism method. Thirty patients were studied with TSH-R BAb M, and 28 with IM. The data were analyzed and compared with our previous results from 88 Graves' patients, 46 Hashimoto patients, and 186 control subjects. Overall, 192 patients with 4 autoimmune thyroid disorders showed a decrease in -Aw19 and an increase in -DQw4 (corrected P < 0.05) and significant associations of -Aw33, -Bw46, -Cw3, -DRw8, -DR9, and -DQw3. In TSH-R BAb M patients, increases in -B35, -Bw60, and -Dw8 and decreases in -DR4 and -DPw2 were seen, whereas IM patients showed increased -DPw2, -Bw61, and -Dw23. In comparisons between TSH-R BAb M and IM, the difference in -DPw2 was highly significant. HLA-B35 differed significantly in these 2 types of hypothyroidism. In conclusion, TSH-R BAb M patients have decreased frequency of -DPw2 and are genetically similar to Graves' disease, whereas IM patients are characterized by high frequency of -DPw2 and are genetically similar to Hashimoto's thyroiditis.

Adult↗
PubMed1983

Expression of cell surface antigens during allogeneic response studies with monoclonal antibodies to a polymorphic marker of activated lymphocytes and HLA class I and class II antigens.

The kinetics of expression of cell surface antigens were studied during allogeneic stimulation and compared to 3H-thymidine incorporation. Two markers of T cell activation identified by monoclonal antibodies (monomorphic HLA-DR and a polymorphic blastic antigen) were compared to an ubiquitous antigen (beta 2m). beta 2m (Class I) and DR (Class II) antigens showed enhanced expression on alloactivated lymphocytes while the blastic antigen was only detected on alloactivated lymphocytes from serologically positive donors. The increased expression of these antigens could distinguish positive and negative mixed lymphocyte reactions and they preceded the rise in 3H-thymidine uptake.

Antibodies, Monoclonal↗
PubMed1990

Restriction fragment length polymorphism (RFLP) of two HLA-B-associated transcripts (BATs) genes in healthy Danes.

The restriction fragment length polymorphism (RFLP) of the two human HLA-B-associated transcripts (BATs) genes, BAT1 and BAT2, was investigated using 5 different restriction enzymes and two human BAT1 and BAT2 cDNA probes. Two of the enzymes, NcoI and RsaI, revealed polymorphic patterns which were investigated in healthy Danes. The cDNA/restriction enzyme combination BAT1/NcoI identifies polymorphic bands at 12 kb, 8 kb, 2.5 kb, and 1.1 kb, while the BAT2/RsaI combination identifies polymorphic bands at 3.3 kb, 2.7 kb, 2.3 kb, and 0.9 kb. The frequencies of these markers were determined in 90 unrelated Danes. Co-dominant segregation and allelic behavior was seen for the BAT1/NcoI 12 kb and 8 kb bands and the BAT2/RsaI 2.7 kb and 2.3 kb bands, respectively. It is possible that the BAT2/RsaI 3.3 kb band represents a rare allele of the BAT2/RsaI system. The BAT2/RsaI 2.3 kb marker was strongly negatively associated with HLA-B8 and HLA-DR3 while there were no strong associations between the BAT1 and BAT2 markers, but the BAT2/RsaI 2.7 kb marker was strongly positively associated with the TNF alpha/NcoI 5.5 kb marker, which in turn is positively associated with HLA-B8 and HLA-DR3. The negative associations between the BAT2/RsaI 2.3 kb marker and HLA-B8 and HLA-DR3 raise the question as to whether this BAT allele may play a role in protecting against certain autoimmune diseases.

DNA Probes, HLA↗
PubMed2000

Associations between HLA-DQB1 high-risk alleles and type I diabetes do not depend on cytomegalovirus antibody status at onset: a case-parent study conducted in Chile.

The purpose of the present study is to ascertain whether the associations between HLA-DQB1*0201 and DQB1*0302 alleles and childhood diabetes depend on the presence of antibodies to human cytomegalovirus (CMV). A study of incident type I diabetes cases and parents was conducted in Santiago, Chile. HLA-DQB1 polymorphisms were determined in 85 case-parent trios (255 subjects), while the detection of CMV was carried out only in the incident cases. As expected, HLA-DQB1 polymorphisms are strongly associated with type I diabetes, with crude odds ratios of 3.7 (95% confidence interval (CI) 1.8-7.7) for the DQB1*0201 allele and 10.3 (95% CI 5.0-21.4) for the DQB1*0302 allele. In the subset of families with CMV+ cases, the odds ratios were estimated as 3.7 (95% CI 1.6-8.6) for the DQB1*0201 allele and 11.1 (95% CI 4.8-25.8) for the DQB1*0302 allele. In families with patients who tested negative for CMV antibodies, the odds ratios were calculated as 3.5 (95% CI 0.7-16.8) for the DQB1*0201 allele, and 8.0 (95% CI 1.8-34.7) for the DQB1*0302 allele. There was no evidence of statistical interaction between CMV antibodies and the DQB1*0201 allele (P value = 0.9) or the DQB1*0302 allele (P value = 0.7). In conclusion, alleles DQB1*0302 and DQB1*0201 do not display distinct associations with type I diabetes depending on the presence of antibodies for CMV.

Adolescent↗
PubMedDate not supplied

Molecular polymorphism of various HLA-D subregions and rheumatoid arthritis.

In Caucasian populations, rheumatoid arthritis (RA) is generally associated with serologic HLA-DR4 specificity. In order to refine this correlation in the HLA-D region, we used six different probes pertaining to this locus: DR beta, DQ beta, DQ alpha, DO beta, DP beta and DP alpha. In this step, pooled RA and control DNA were hybridized with DR beta and DQ beta probes after digestion with 12 different endonucleases. Some bands appeared specific in the RA pool. In fact, with genomic DNA from 13 unrelated typed RA patients and 12 matched or partially matched control cells, these bands were revealed to be related to DR4 and/or DR1, with DR beta and DQ beta probes hybridizing BamHI, EcoRV, PvuII and StuI digests. With other probes, no differences could be related to RA disease. The polymorphism detected by these probes was suggestive of a gradient of decreasing complexity from DR beta to DO beta through DQ beta and DP beta, which could reflect discrete functions of each subregion.

Arthritis, Rheumatoid↗
PubMedDate not supplied

HLA-A, B and C polymorphisms in three major populations living in South Africa.

The HLA class I antigen gene and haplotype frequencies of three major population groups living in the Transvaal province of South Africa were determined. The HLA-A, B and C antigens were tested in 877 South African Negroids, 381 Coloured and 771 Caucasoids. Differences in gene and haplotype frequencies between the various populations were observed. HLA-A11 appears with a low frequency in the Negroids (gf = 0.004) and the Caucasoids revealed an absence of HLA-Bw70. The frequencies of the HLA antigens in the Coloured population were generally intermediate between those of the other two groups. The most frequent haplotypes were A3, B7; A30, B8 and A2, B58 in the Caucasoids, Negroids and Coloured respectively. Genetic distance analysis reveals that Negroids and Caucasoids are distinct groups and the Coloured occupy an intermediate position.

Black People↗
PubMed1993

The different level of expression of HLA-DRB1 and -DRB3 genes is controlled by conserved isotypic differences in promoter sequence.

HLA-DRB1 and -DRB3 are two genes encoding two distinct HLA-DR beta chains in the DRw52 family of haplotypes (DR3, DR5, DR13, and DR14). These beta chains determine the structural and functional identity of the two kinds of HLA-DR molecules expressed. The highly polymorphic HLA-DRB1 locus is always expressed at a higher level than the HLA-DRB3 locus, and functional assays indicate that the proximal promoter of DRB1 is indeed more active than that of DRB3. The DNA sequence of the two promoters in nine different DRw52 haplotypes has revealed a stricking allelic conservation as well as characteristic, isotype-specific, conserved-sequence motifs. These isotype-specific differences concern the functionally essential X and Y box motifs of HLA class II promoters, and they do indeed affect binding of specific nuclear factors to the X and Y boxes of DRB1 or DRB3 promoters. Finally, analysis of the activity of various normal and mutated DRB1 or DRB3 promoters indicates that the X box region of these promoters plays a dominant role in controlling the relative levels of HLA-DRB1 and -DRB3 gene expression.

Alkaline Phosphatase↗