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Results for “HLA polymorphism”

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At least 253 records · Page 14Linked to original sources

PubMed2006

Frequency of CTLA-4 gene CT60 polymorphism may not be affected by vitamin D receptor gene Bsm I polymorphism or HLA DR9 in autoimmune-related type 1 diabetes in the Japanese.

One of the CTLA-4 SNPs, +6230G>A (CT60), has recently been reported to be related to susceptibility to type 1 diabetes and autoimmune thyroid disease. We have previously reported an association between acute-onset type 1 diabetes in Japanese and the Vitamin D receptor (VDR) gene Bsm I large B polymorphism, which is related to the Th1-type response. Moreover, we found a significant correlation between autoimmune-related type 1 diabetes with HLA DR9 and detection of GAD-reactive Th1 (T helper 1)-type cells. In the present article, we tried to clarify whether the frequency of one of the CTLA-4 SNPs, +6230G>A (CT60), is affected by the VDR gene Bsm I polymorphism or by HLA DR9 in Japanese type 1 diabetics. The frequency of the CT60 GG genotype did not appear to be affected by either the VDR gene Bsm I large B polymorphism or HLA DR9.

Adult↗

PubMedDate not supplied

New HLA DNA polymorphisms associated with autoimmune diseases.

Certain class II determinants of the human histocompatibility locus antigens (HLA) have been implicated in the aetiology of several autoimmune diseases, including rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM). HLA-Dw4 was the first HLA determinant found to be significantly increased in RA patients compared with controls, while Dw4 and Dw3 were found to be significantly increased in IDDM patients. When the HLA-DR system was defined, RA patients were found to have an increased frequency of DR4 and IDDM patients an increased incidence of both DR4 and DR3 compared with controls. As the HLA-Dw specificities are narrower than the serologically defined DR specificities, it was of specific interest to the present study that Dw4, Dw10, Dw13, Dw14, Dw15 and DKT2 are included in DR4. We describe here new restriction fragment length polymorphisms (RFLPs) and, together with the newly described serologically defined DQ specificity TA10, test their prevalence and associations in controls and diseased patients. We find that the newly characterized DNA bands are present at a much higher frequency in RA and IDDM patients than in controls. These findings may lead to a greater understanding of the pathogenesis of such diseases.

Arthritis, Rheumatoid↗

PubMed1999

Molecular studies of trophoblast HLA-G: polymorphism, isoforms, imprinting and expression in preimplantation embryo.

There is considerable interest in human HLA-G arising from the observation that it is expressed selectively on the surface of extravillous trophoblast, the fetal cell population directly in contact with the mother. We investigated several aspects of the molecular biology of this unusual molecule. Limited polymorphism at the nucleotide level, and even more restricted variation at the amino acid level, was found in our Caucasian population. A further unusual aspect of HLA-G is the occurrence of alternatively spliced mRNAs. Spliced messages that could give rise to either membrane-bound or soluble proteins have been reported and six of these alternative forms were detected in all first trimester and term placentae, highly purified villous and extravillous trophoblast and the cell lines, JEG-3 and 221-G. An additional novel splice variant involving loss of part of the 3'-untranslated region was observed with two alleles. Using a sensitive RNase protection assay higher levels of the membrane-bound RNAs as compared to the soluble forms were detected in first trimester and term placentae as well as in JEG-3. Contrary to previous findings our term samples taken from the maternal aspect showed higher levels of both mRNA species when compared to first trimester placenta. The question of imprinting was addressed through the detection of heterozygotes both in placental tissue and, more tellingly, in the purified trophoblast cells. There was no evidence of imprinting. In addition we did not find mRNA for HLA-G in human two to eight-cell embryos or in blastocyst or in sperm samples.

Alleles↗

PubMed2002

HLA-DR and HLA-DQ polymorphism in human thyroglobulin-induced autoimmune thyroiditis: DR3 and DQ8 transgenic mice are susceptible.

In contrast to H2-based susceptibility to experimental autoimmune thyroiditis (EAT) induced with thyroglobulin (Tg), human leukocyte antigen (HLA) association with Hashimoto's thyroiditis, the human counterpart, is less clear, and determining association is further complicated by DR/DQ linkage disequilibrium. Previously, we addressed the controversial implication of HLA-DR genes by introducing HLA-DRA/DRB1*0301 (DR3) transgene into endogenous class II negative H2Ab(0) mice. EAT induction with either human (h) or mouse (m) Tg demonstrated the permissiveness of DR3 molecules for shared Tg epitopes. Here, we examined the participation of HLA-DQ genes by introducing DQA1*0301/DQB1*0302 (DQ8) transgene into class II negative Ab(0) or class I and II negative beta(2)m((-/-)) Ab(0) mice. About 50% and 80% of HLA-DQ8(+) Ab(0) and beta(2)m(-) Ab(0) mice, respectively, developed moderate EAT after hTg immunization, but only minimal response to mTg. The hTg presentation to hTg-primed cells was blocked by anti-DQ mAb in vitro. By contrast, HLA-DRB1*1502 (DR2) and *0401 (DR4) transgenes contributed little to hTg induction. Similarly, DQA1*0103/DQB1*0601 or DQA1*0103/DQB1*0602 (DQ6) transgenic Ab(0) mice were unresponsive to hTg induction and carried no detectable influence in DQ8/DQ6 double transgenic mice. Thus, both HLA-DR and -DQ polymorphism exists for hTg in autoimmune thyroiditis. The use of defined single or double transgenic mice obviates the complications seen in polygenic human studies.

Animals↗

PubMed1995

[HLA DRB1 polymorphism in rhizomelic pseudo-polyarthritis and Horton disease].

Some studies have suggested that distribution of HLA DRB1 alleles in polymyalgia rheumatica (PMR) resembles that found in giant cell arteritis (GCA). However these data are controversial. OBJECTIVE--To evaluate in French native patients whether PMR immunogenetically resembles GCA in determining HLA DRB1 alleles. PATIENTS AND METHODS--Fourty-five patients were included in the study. Twenty-one patients with PMR alone (Bird's criteria) and 24 with GCA (ACR criteria). In 11 patients, GCA was associated with PMR. HLA DRB1 genotype was determined by PCR-RFLP analysis. Statistical analysis was performed by the chi 2 test and determination of the odds ratio (OR). Two hundred and thirty-three unselected normal healthy subjects served as controls. RESULTS--A significant increased prevalence of HLA DR1 was observed in patient with PMR alone and an absence of DR7 (0% vs 10.3%, p = 0.02, OR = 0.1). An increased incidence of DR4 and particularly *0401 allele was only found in patients with GCA (OR = 2.4). No patient with isolated PMR had DR7 genotype compared with 25% in GCA (p < 0.001, OR = 0.03). A comparative study between isolated PMR versus GCA showed a significant increased in DR1 and DR3 alleles in isolated PMR and a significant increased prevalence of DR4 and DRB1 *0701 allele in GCA. CONCLUSION--The present study emphasizes the absence of similarity in HLA DRB1 allele distribution between PMR and GCA. The association of DR7 in patient with GCA seems characteristic in French native patients.

Aged↗

PubMed1991

DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis.

We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 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: DRB1*08 (DRw8) (35.2% vs 10.3%, RR = 4.6, p less than 10(-3), DRB3*01/02/03 (DRw52) (76.3% vs 48.1%, RR 3.5, p less than 10(-3)), DQA1*0401 (41.0% vs 7.4%, RR = 7.9, p less than 10(-3)), DQA1*0501 (55.6% vs 29.7%, RR = 3.0, p less than 10(-2), DQB1*0301 (DQw7) (46.2% vs 17.5%, RR = 4.0; p less than 10(-2)), DPA1*0201 (44.2% vs 7.9%, RR = 8.7, p less than 10(-5)), and DPB1*02 (DPw2) (40.7% vs 7.1%, RR = 8.5, p less than 10(-6)). The frequency of DRB1*11 was 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: DRB1*04 (14.8% vs 40.2%, RR = 0.27; p less than 10(-3)), DRB1*07 (0% vs 25.9%, RR = 0.04, p less than 10(-3)), DRB4*0101 (DRw53) (25.9% vs 53.6%, RR = 0.31, p less than 10(-3)), DQA1*0102 (11.6% vs 36.0%, RR = 0.25, p less than 10(-4)), and DQA1*0201 (2.6% vs 34.2%, RR = 0.05, p less than 10(-2)).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Juvenile↗

PubMed2002

[Association of hypersensitivity to wormwood pollen in patients with allergic rhinitis with HLA alleles polymorphism].

OBJECTIVE: Our purpose was to determine whether alleles at one or more HLA loci are associated with hypersensitivity to wormwood pollen in patients with allergic rhinitis. METHOD: By using PCR-SSP(sequence-specific primer polymerase chain reaction), we tested the frequency distribution of HLA-DQA1, DQB alleles in 41 patients with allergic rhinitis(AR) and 41 healthy controls from Beijing. RESULT: The frequency of HLA-DQA1* 0201, DQB1 * 0602 was lower in AR than in controls(24.39%, 4.88% vs 46.34%, 26.83%), and the frequency of DQA1 * 0302 was increased among patients(58.54% vs 14.63%). CONCLUSION: HLA-DQA1 * 0201, DQB1 * 0602 alleles might confer protection against AR, and DQA1 * 0302 may be a susceptibility factor for hypersensitivity to wormwood pollen.

Adolescent↗

PubMed1984

Two-dimensional gel analysis of a second family of class II molecules by polymorphic HLA-DR4,5, and w9 monoclonal antibodies.

Human Ia-like, class II molecules were isolated by immunoprecipitation with monoclonal antibodies from various HLA-D/DR homozygous cell lines and were analyzed by two-dimensional gel electrophoresis. The monoclonal antibody PLM12 reacted with B cells carrying DR4, DR5, DRw6.2, and DRw9 phenotypes, and its reactivity perfectly correlated with the previously defined TB21 (MB3-like) specificity. Class II molecules detected by PLM12 were structurally distinct from those precipitated by the anti-DR monoclonal antibody NC1 on all HLA-DR4, DR5, DRw6.2, and DRw9 homozygous cell lines and showed polymorphism in heavy and light chains among these cell lines. The monoclonal antibodies PLM2 and PLM9 only reacted with B cells carrying DR5 and DRw6.2 and also detected a distinct set of class II molecules from those precipitated by NC1 but identical to those of PLM12. Thus, PLM2 and PLM9 serologically detected a new subtypic antigen of the PLM12-reactive class II molecules. Furthermore, the antibody NC1 precipitated two light chains and one heavy chain from HLA-DRw6.2 homozygous cell line EBV-Sh. The result indicated the presence of three sets of class II molecules: two in a DR family and another carrying the polymorphic determinants detected by PLM2, PLM9, and PLM12 in a second family.

Animals↗

PubMed2003

Functional analysis of HLA-DP polymorphism: a crucial role for DPbeta residues 9, 11, 35, 55, 56, 69 and 84-87 in T cell allorecognition and peptide binding.

The information available on the specific function of HLA-DP and the structure-function relationships is very limited. Here, single amino acid substitutions of HLA-DPB1*02012 have been used to analyze the role of polymorphic residues of the DPbeta1 domain on DP-mediated T cell allorecognition and peptide binding. Using a panel of specific anti-HLA-DP mAb, we identified the HLA-DP residues involved in the recognition by these mAb, with a crucial role for DPbeta56 for most of the mAb assayed. Individual substitutions at residues 9, 11, 35, 55, 56 and 69 completely abrogated T cell recognition mediated by two different HLA-DPw2-allospecific T cell clones (8.3 and 8.9). Interestingly single changes at positions 9, 11, 35 and 55 of HLA-DPbeta also altered the binding of peptides AAII(12-27) and IIP(53-65), natural ligands of the HLA-DPB1*02012 molecule. Individual changes at residues located in pocket 1 (84, 85, 86 and 87 from HLA-DPbeta) led to a partial reduction in cytotoxic T lymphocyte-mediated lysis and also partially affected peptide binding. However, the simultaneous substitution of these positions completely abolished both T cell allorecognition and peptide binding, suggesting a major role for polymorphisms at pocket 1 in HLA-DP function. Molecular modeling, used to predict changes induced by amino acid substitutions, supported the functional data. Taken together, these results strongly suggest that polymorphic residues 84, 85, 86 and 87 at pocket 1, residues 9, 35 and 55 at pocket 9, and residues 11 and 69 at pockets 6 and 4 respectively play a key role in HLA-DP function, probably by modifying the way the peptide is bound within the groove of HLA-DP2 and determining changes in the conformation of the MHC-peptide complex recognized by the TCR.

Antibodies, Monoclonal↗

PubMed1992

HLA-DP polymorphism in Sudanese controls and patients with insulin-dependent diabetes mellitus.

Human leukocyte antigen (HLA) genes are candidates for susceptibility to insulin-dependent diabetes mellitus (IDDM). The association of IDDM with particular DR and DQ alleles has been reported in all populations studied, but its association with HLA-DP alleles has been controversial. To address this question we analyzed 19 DPB1 and 2 DPA1 alleles and their associations in well-characterized Sudanese (an admixture of Arab and Black) IDDM patients (n = 71) and ethnically matched controls (n = 86) using polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) typing. There were no significant differences between the patient and control groups in the DPB1 frequencies. DPB1*0201, *0401 and DPA1*01 were the most frequent alleles in both IDDM patients and control subjects. Significant positive and negative associations between DPB1 and DPA1 alleles were detected in both groups. A novel DPB1 allele included in DPB1*1701 was identified.

Alleles↗

PubMed1988

Class II HLA DNA polymorphisms in type 1 (insulin-dependent) diabetic patients of north Indian origin.

Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQ beta and DX alpha DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQ beta/DX alpha pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%, p less than 0.001, relative risk = 5.12 (95% confidence limits: 1.96-13.4)). A DQ beta polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%, p less than 0.02, relative risk = 0.10 (95% confidence limits: 0.02-0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DR beta polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%, p less than 10(-6), relative risk = 12.1 (95% confidence limits: 4.32-33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.

Diabetes Mellitus, Type 1↗

PubMed2004

HLA-DP polymorphism in Venezuelan Amerindians.

Three different Venezuelan Amerindian tribes were studied for human leukocyte antigen (HLA)-DPA1 and DPB1 allelic variability using polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and sequence-based typing in a selected group of samples. These tribes are geographically (two from the Perija Mountain range and one from the Orinoco Delta) and linguistically distinct: the Bari (from Campo Rosario and Saymaidoyi villages) and the Warao have been classified within the Chibcha linguistic family, whereas the Yucpa (from the Aroy, Marewa, and Peraya villages) are Carib speaking. Venezuelan Indians, like other Native American tribes, show a markedly reduced number of different HLA-DP alleles (range, 2-7) and haplotypes (range, 4-11) in comparison with neighboring Venezuelan mestizo and other non-Indian populations. Some HLA-DPB1 (*0402 and *1401) alleles characteristic for all Amerindian tribes are present also in these populations. Despite general similarities, each tribe and, in some cases, some subtribes show their own pattern of allele and haplotype distribution apparently more as a result of linguistic than to geographic variation.

Alleles↗

PubMed2006

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study.

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Aortic Aneurysm, Abdominal↗

PubMed1995

HLA-DPB1 polymorphism in patients with rheumatoid arthritis in Taiwan.

OBJECTIVE: To investigate the role of HLA-DP alleles in the pathogenesis of rheumatoid arthritis (RA). METHODS: HLA-DPB1 alleles were studied in 144 patients with RA and 144 healthy controls using the polymerase chain reaction/sequence specific oligonucleotide probe method. RESULTS: HLA-DPB1*0510 was the the most common allele in patients with RA and healthy controls in Taiwan. There was no significant difference in frequencies of HLA-DPB1 alleles between patients and controls. The HLA-DPB1 alleles were not associated with seropositivity for rheumatoid factor, extraarticular involvement, or bone erosion in patients. There was also no significant difference in frequencies of HLA-DPB1 alleles among DR4-positive and DR4-negative patients and controls. CONCLUSION: There was no significant difference in the prevalences of HLA-DPB1 alleles between Taiwanese patients with RA and healthy controls. HLA-DPB1 alleles were not related to the clinical manifestations of patients with RA in Taiwan.

Alleles↗

PubMed2006

Polymorphism of HLA-DR and HLA-DQ in rheumatoid arthritis patients and clinical response to methotrexate--a hospital-based study.

OBJECTIVE: To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis (RA) and analyze the relationship between clinical response to methotrexate (MTX) and the HLA-DR and HLA-DQ genotypes in these patients. METHODS: In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers. RESULTS: There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common (p=0.015) in RA patients compared to controls. HLA-DRB1*15 was more common in patients (43.5%) compared to controls (30.8%) but results were not significant. HLA-DRB1*08 and DRB1*09 were present in negligible number in patients as well as controls while HLA-DRB1*12 was conspicuously absent in controls. Similarly, DQB1*06 was also significantly more common (p = 0.01) among the patients compared to healthy control subjects, while there was no statistical difference in the frequencies of DQB1*02, DQB1*03, DQB1*04 and DQB1*05 among the cases and the controls. RA susceptibility in most patients appeared to be associated with the HLA-DRB1*01/DQB1 *06 genotype. Regarding association between HLA-DR or HLA-DQ genotype and clinical response to methotrexate (MTX), the data showed that with the exception of HLA-DRB1*03, there appears to be no association between the particular subtypes of HLA-DR and HLA-DQ. HLA-DRB1*03 was significantly-more common among non-responders to MTX alluding to the possibility that another genes responsible for MTX metabolism, might be in linkage disequilibrium with HLA-DRB1*03 in the Pakistani population, thereby making such individuals non-responsive to MTX-therapy. CONCLUSION: RA susceptibility in most Pakistani patients is associated with the HLA-DRB1*01/DQB1*06 genotype. HLA-DRB1*03 was found to be significantly more common among non-responders to MTX treatment suggesting that Pakistani patients with this genotype are less likely to benefit from MTX.

Adult↗

PubMed1995

Distribution of the HLA-DQA1 polymorphism in the population of the Basque Country (Spain).

Allele and genotype frequencies at the HLA-DQA1 locus were determined in Basque Country populations using PCR methodology and a dot-blot assay with ASO probes. The results showed no deviation from the Hardy-Weinberg equilibrium. No differences were found between the three Basque Provinces, but gene frequencies were significantly different from those of some other Spanish and world populations.

Alleles↗

PubMed2003

DNA typing revealing high HLA-Cw polymorphism completes availability of major histocompatibility complex loci in forensic medicine.

Studies of human population genetics in Hungary have revealed relevant heterogeneity in the major histocompatibility complex. In the present studies, two isolated ethnic groups were chosen: people living in the Káli Basin westward from the Danube River, and those living in Opusztaszer, a village eastward from Danube, who are known as native ancient Hungarians. Blood samples were collected from 70 people in the Káli Basin and from 45 people in Opusztaszer. The frequency of HLA-Cw alleles was determined by serology as well as by DNA typing in 46 and 32 samples of the two populations, respectively, and in 44 randomly selected subjects of Hungarian origin. Compared with a random population of cadaver donors (the deaths having resulted mostly from accidents or, in a smaller number, strokes or heart infarcts) and voluntary bone marrow donors (typed in the last 10 years) recruited from all parts of Hungary and representing the mixed Hungarian population, remarkable differences were found in haplotype and allele frequencies. HLA-A, -B, -Cw typing was performed by serology and, in the case of the HLA-Cw locus, by polymerase chain reaction (PCR)-SSP and/or PCR-SSOP techniques, as well. The PCR-SSO oligotyping procedure allowed the identification of 32 Cw alleles in contrast with the 9 serologically detectable types. Because of the combination of low antigen expression and the lack of specific serologic reagents of good quality, no HLA-Cw antigens were detectable in 41%, and only one was detected in 48%, of the investigated individuals by standard serologic typing. With PCR-SSO typing, however, 97% of the investigated individuals proved to be heterozygous for HLA-Cw alleles. The two isolated populations differed from each other, from mixed Hungarian and other Caucasian populations in HLA-Cw* allele frequencies, as well as in haplotype distribution. This newly recognized polymorphism at the HLA-Cw locus completes the availability of major histocompatibility complex typing in forensic science and practice.

Cadaver↗

PubMed1987

HLA-DQ beta-chain polymorphism in HLA-DR4 haplotypes associated with rheumatoid arthritis.

With a cDNA probe for the DQ beta gene, two variants of the DR4-linked DQw3 (3.1 and 3.2) allele were analysed in patients with rheumatoid arthritis (RA), healthy individuals, and homozygous cell lines. The DQw3.1 allele, identified by 3.4 kb (HindIII), 2.3 kb (SstI), and 3.7 kb and 6.9 kb (BamHI) restriction fragment lengths, was expressed in 100% (of 18) DR4-positive patients, compared with only 19% (of 16) of DR4-positive controls including one of five homozygous cell lines. This DQ beta variant showed a highly significant association (relative risk = 78; p less than 10(-6) with RA and may therefore play an important part in susceptibility to RA.

Arthritis, Rheumatoid↗