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Results for “HLA polymorphism”

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At least 613 records · Page 34Linked to original sources

PubMed2002

Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid arthritis: a prospective longitudinal study.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic synovitis leading to permanent damage of the joints. Collagenase-1 (MMP-1) is a matrix metalloproteinase involved in articular cartilage degradation. We investigated the association between a biallelic polymorphism in the MMP-1 gene promoter and the susceptibility to, and severity of, RA. We also investigated the association between HLA-DRB1 gene polymorphism and severity of RA. METHODS: One hundred and three patients with early RA were included in this prospective longitudinal study. A radiographic damage score was used to quantify disease severity at baseline and after 4 years of followup. MMP-1 polymorphism genotyping was analyzed using a fluorescent-based polymerase chain reaction (PCR). HLA-DRB1 genotypes were determined by PCR sequence-specific oligonucleotide probes. One hundred and thirty-three healthy individuals were used as controls. RESULTS: MMP-1 allele and genotype frequencies did not differ between RA patients and controls. The radiographic damage or its progression over the 4 years of followup did not differ across MMP-1 genotypes. The radiographic damage score and its progression over the 4 years of followup differed across HLA-DRB1 genotypes. The HLA-DRB I shared epitope +/+ genotype was associated with the highest radiographic damage score and the highest progression, while the shared epitope -/- genotype was associated with the lowest. CONCLUSION: Our results do not support the hypothesis of an association between this particular polymorphism in the MMP-1 gene promoter and susceptibility to, or severity of, RA. This study confirms the previous reports of an association between the HLA-DRB1 gene polymorphism and severity of RA.

Adult↗

PubMed2004

[Study on the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes in Yunnan Han nationality].

OBJECTIVE: To investigate the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes mellitus in Yunnan Hans. METHODS: Polymerase chain reaction-sequence specific primers(PCR-SSP) genotyping method was conducted in 108 Han patients with type 2 diabetes and 56 ethnically matched controls from the same area of Yunnan Province. RESULTS: HLA-DQA1*0301(RR=3.092, P<0.01) and DQA1*0501 (RR=3.257, P<0.05) allelic frequencies in type 2 diabetic patients were significantly higher than those in non-diabetic control subjects respectively. HLA-DQA1*0401 (RR=0.371, P<0.01) allelic frequencies in patients were significantly decreased, compared with controls; HLA-DQA1*0302 (RR=3.356, P<0.01) allelic frequencies in patients with type 2 diabetic nephropathy were significantly increased. CONCLUSION: HLA-DQA1*0301 and DQA1*0501 are susceptible genes of type 2 diabetes in Yunnan Han nationality; in reverse, HLA-DQA1*0401 is a resistant gene. HLA-DQA1*0302 is a susceptible gene of type 2 diabetic nephropathy.

Adult↗

PubMed1993

Deficient tumor-infiltrating T-lymphocyte response in malignant lymphoma: relationship to HLA expression and host immunocompetence.

Tumor-infiltrating T-lymphocytes (T-TIL) are putative mediators of tumor containment that exhibit unique specificity for autologous tumor cells. The magnitude of T-TIL response in biopsy specimens from patients with B-cell lymphoma has been suggested as an independent predictor of clinical outcome. Since recognition of tumor antigens may occur in association with major histocompatibility complex (MHC) molecules, effective T-TIL tumor immunosurveillance may be limited by either failure to express MHC-encoded recognition structures and/or host T-cell immunocompetence. To further delineate T-cell immunoregulation in B-cell lymphoma, we assessed T-TIL fraction and tumor expression of invariant class I and class II HLA determinants by immunohistochemistry in biopsy specimens. Two distinct clinical cohorts of B-cell lymphoma were investigated to delineate pathogenetic differences in T-TIL response. One group, representing immunodeficient and transplant-related lymphomas, comprised 18 patients with AIDS- or allograft-related lymphoma. The second group comprised 83 consecutive cases of sporadic diffuse large cell (DLCL) lymphoma. Median CD8+ T-TIL was significantly lower (4.9% versus 12.7%) among immunodeficiency-associated lymphoma and the frequency of cases with low (< 6%) CD8+ T-TIL greater (76% versus 23%) (p < 0.0001). None of the immunodeficiency-associated lymphomas demonstrated non-polymorphic HLA loss. Absence of one or more class I or II HLA determinants was found in 13 out of 19 (68%) sporadic DLCL specimens with low CD8+ T-TIL, compared to 20% of cases with higher T-TIL fraction (p = 0.0004). These findings implicate impaired host immunosurveillance in deficient T-TIL response in immunodeficiency-associated B-cell lymphoma, whereas low T-TIL in sporadic cases of DLCL relates to tumor loss of HLA determinants. Strategies to modulate tumor HLA expression or augment antitumor response merit investigation in patients with B-cell lymphoma.

Adolescent↗

PubMed2001

Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class II haplotypes.

Infection with high-risk human papillomavirus (HPV) is necessary for the development of a cervical lesion, but only a fraction of precursor lesions progress to cancer. Additional factors, other than HPV type per se, are likely to increase the probability for progression. Intratype genome variations have been reported to be associated with viral persistence and the development of a major cervical disease. We have recently shown that the prevalence of specific HPV16-E6 variants in invasive cervical cancer (ICC) varies between Italian and Swedish women. To extend our initial study we have analyzed E6 variants in cervical lesions from Czech women, ranging from low-grade cervical intraepithelial neoplasia (LCIN) to ICC and scaled up the sample size of our initial study of Swedish and Italian women. In addition, we have correlated the cases of cancers with human leukocyte antigen (HLA) class II haplotypes. In line with our earlier observation, the distribution of specific HPV16-E6 genotypes in CIN and ICC varied in the 3 cohorts. For instance, the HPV16-E6 L83V variant, which has been found to be positively associated with ICC in Swedish women (p = 0.002), was more prevalent in LCIN than in ICC in Italian and Czech women (p = 0.01 and = 0.03, respectively). These data indicate that host genetic factors, such as HLA polymorphism, may determine the potential oncogenicity of the HPV16-E6 L83V variant. Indeed, the DR04-DQ03 haplotype, which is approximately 3-fold more abundant in the normal Swedish population than in those in Italy and the Czech Republic, was found to be positively associated with HPV16-E6 L83V in the 3 cohorts investigated (p = 0.01). This observation may explain why L83V is a risk factor more in Sweden than in the other 2 countries.

Cross-Sectional Studies↗

PubMed2003

[Study on the genic polymorphism of HLA-DRB1 in a population in the north of China].

OBJECTIVE: To investigate at the DNA level the polymorphism of HLA-DRB1 gene in Han population in Beijing of China. METHODS: This study was conducted in the Hans in Beijing. A total of 2810 normal and unrelated neonates were analyzed and subjected to HLA-DRB1 low resolution typing, and from among them 217 neonates were randomly selected for DRB1 high resolution typing by polymerase chain reaction-sequence specific primers technique. RESULTS: Fourteen HLA-DRB1 specificity and 39 alleles were found with HLA-DRB1 *09012, *1501, *07011, *08032 as the most common genes. Their gene frequencies and allelic distributions were compared to those observed in other ethnic populations. CONCLUSION: The results showed the characteristic of HLA-DRB1 distribution, and provided more comprehensive and accurate gene data that may serve as normal reference values for the population in Beijing, China.

Asian People↗

PubMed1999

HLA-B locus sequence-based typing.

We describe an approach for HLA-B high-resolution typing. A single locus-specific amplification generates a 1-kb fragment useful for direct sequencing. Four internal primers are necessary for exon 2 and 3 cycle-sequencing in both directions. Fluorescent dye-labelled nucleotides are incorporated during cycle-sequencing and reaction products are analyzed in an automated DNA sequencer. At present, software programs allow automatic assignment of exon 2 only; analysis of exon 3 is not automatic. In the future, the development of more sophisticated software will improve allele assignment. The approach described in this work offers a precise and efficient identification of known allele sequences and at the same time can differentiate new alleles. Furthermore, it may be applied as a model for the development of similar molecular typing approaches for other polymorphic HLA loci.

Alleles↗

PubMed2004

High frequency of TNF alleles -238A and -376A in individuals from northern Sardinia.

The G to A single nucleotide polymorphisms (SNPs), at position -376, -308 and -238 in the promoter of the tumor necrosis factor alpha (TNF) gene, have been independently correlated with numerous diseases. Alleles TNF(-376A) and TNF(-238A) are normally found throughout the world with very low frequencies. We investigated the frequency of these SNPs in Sicilian subjects hospitalized after traumatic brain injury and in three groups of subjects from northern Sardinia: healthy subjects and individuals with multiple sclerosis or ischemic stroke. While no significant difference was found between healthy and disease subjects, the frequency of TNF(-376A) and TNF(-238A) was elevated up to 10 times in Sardinia compared to Sicily and other populations throughout the world. These elevated frequencies may be the result of genetic drift or of selective pressure on TNF itself or on neighboring genes, including the HLA. Malaria, endemic to Sardinia until the end of the 1940s, and the bubonic plague, are among the possible causes of selection. These findings indicate that Sardinia is an ideal location to further elucidate the correlation between TNF or HLA polymorphisms and diseases, including multiple sclerosis and type-I diabetes, present with an unusually high frequency and co-morbidity in Sardinia.

Diabetes Mellitus, Type 1↗

PubMed2006

Suppressed cellular alloimmune responses in HIV-exposed seronegative female sex workers.

Particular human leucocyte antigen (HLA) polymorphisms have been associated with a reduced risk of HIV transmission. However, protective alloimmune responses expected to result from such a genetic predisposition have not been demonstrated. To this end, we analysed and compared cellular and humoral alloimmune responses in a cohort of female sex workers who remained human immunodeficiency virus (HIV)-seronegative despite more than 3 years of high-risk sexual activity (ESN FSWs) with those of low-risk HIV-seronegative female blood donors in Abidjan, Côte d'Ivoire. ESN FSWs showed significantly lower allostimulated CD69 expression and secretion of interferon-gamma, macrophage inflammatory protein (MIP)-1beta and RANTES (regulated upon activation, normal T-cell expressed and secreted) by lymphocytes than controls. In contrast, ESN FSWs showed significantly higher mitogen-stimulated CD69 expression and secretion of tumour necrosis factor-alpha and MIP-1beta than controls. Suppression of cellular alloimmune responses among ESN FSWs was associated with a higher self-reported frequency of unprotected sex. Levels of anti-HLA class I alloantibodies in plasma were not significantly different between ESN FSWs and controls. These findings indicate that frequent sexual exposure to multiple partners results in suppression rather than activation of cellular alloimmune responses. Our data support the hypothesis that suppressed cellular alloimmune responses may play a role in protection against HIV infection.

Adult↗

PubMed2000

HLA-DRB1 gene polymorphism in patients with dilated cardiomyopathy.

To probe into the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM), HLA-DRB1 gene polymorphism in 68 patients with DCM and 175 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) techniques. It was found that the frequencies of HLA-DRB1* 15 and HLA-DRB1* 03 alleles were significantly lower in DCM patients than those in normal controls (14.71% vs 29.71% and 4.41% vs 15.43%, respectively), the relative risks (RR) in the DCM patients being 0.41 and 0.25, respectively, all P < 0.05. However, the frequencies of HLA-DRB1* 11 and HLA-DRB1* 12 alleles were significantly higher in the DCM patients than in controls (29.4% vs 12.00% and 36.76% vs 12.57%, respectively) with the RR in the DCM patients being 3.06 and 4.04, respectively, all P < 0.01. These findings further demonstrated that immunogenetics might play a predominant pathogenetic role in partial DCM patients.

Adult↗

PubMed1982

[The propensity to malignant changes in heterozygous moles].

There are at least two mechanisms of origin for complete mole, each with different genetic implications; 1) the fertilization of an empty egg by a haploid sperm and its subsequent duplication (homozygous mole), 2) the fertilization of such an egg by two haploid sperms, which produces an heterozygous constitution of allelic genes (heterozygous mole). The present study was undertaken to investigate whether the difference of origin would determine whether the moles underwent malignant transformation or not. By using of chromosomal, enzymatic and HLA polymorphisms, 35 moles were confirmed to be androgenetic in origin. Among them fifteen homozygous and 4 heterozygous moles were identified. The persistency of high HCG titration of the urine in the mother was observed in all 4 cases from the latter (4/4-100%), though the percentage of the development of sequelae in the former was low (1/15-6.7%). The diagnosis of destructive mole was established in the uterine lesion of 2 heterozygous moles by pathological examination. These two patients had lung metastases. A high incidence of sequelae after the expulsion of heterozygous moles suggests that the heterozygous constitution of allelic genes plays an important role in the process of malignant transformation of trophoblasts.

Adult↗

PubMed1989

Southern blot analysis of HLA-DP gene polymorphisms in Caucasoid rheumatoid arthritis (RA) patients and controls.

Despite extensive analysis of the incidence of HLA-DR and HLA-DQ allele frequencies in defined autoimmune disease groups, there is very little information available on HLA-DP allele frequencies. This is largely because HLA-DP typing has until recently been restricted to primed lymphocyte typing (PLT). However, allelic polymorphism of the HLA-DP subregion can now be studied by Southern blot analysis or genotyping with DPA1 and DPB1 probes. By direct counting of allele-specific DNA fragments, we have analyzed the frequencies of five major DP genotypes (DPw1, DPw2, DPw3/6, DPw4, and DPw5), in a large number of Caucasoid rheumatoid arthritis (RA) patients (n = 74), and controls (n = 91). The predicted frequency of DP alleles in both patient and control groups was comparable to PLT-determined DP allele frequencies in normal Caucasoids. However, the gene frequency of DPw4 was increased in the RA patients, with 51% of the patients studied scoring as DPw4, 4 homozygotes. With the exception of one possible combination (DPw5 and DRw6) in the controls, no significant linkage disequilibrium was detected between DP and DR alleles in either patient or control groups. Thus the prevalence of DPw4 in the RA patients is independent of any disease association with the DR loci, and may represent a new class II association with RA.

Arthritis, Rheumatoid↗

PubMed1990

CD4+ cytolytic T cell clones that recognize polymorphism of HLA-DR beta 3 chains.

We have investigated HLA-DR beta 3-associated functional polymorphism using selected Epstein-Barr virus (EBV) specific human T cell clones and EBV-transformed B cell (EBV-B) lines. To study the relationship between T cell recognition and the gene products of the three alleles of the DR beta 3 locus, Dw24, 25 and 26 (these were previously called DRw52a, b and c, respectively), CD4+ cytolytic T cell clones (CD4+ CTL) were isolated by repeated stimulation of peripheral blood mononuclear cells (HLA A2 A24; B8 B27; DRw17, Dw24, DRw2) with autologous EBV-B. Clone no. 32 proliferated strongly in response to HLA-Dw24 EBV-B, but not to Dw25 or Dw26 EBV-B. Furthermore, clones no. 32 and no. 45 both lysed HLA-Dw24 EBV-B but not Dw25 or Dw26 EBV-B. In addition, cold target inhibition studies showed that the cytolytic activity of both clones was blocked by unlabelled HLA-Dw24 EBV-B, but not by Dw25 or Dw26 EBV-B. Clones no. 32 and no. 45, therefore, could distinguish between the three allelic products of DR beta 3 haplotypes.

Antigens, Viral↗

PubMed2000

HLA-DMA allele polymorphism: no impact on kidney allograft outcome.

The purpose of this study was to analyze the association of HLA-DMA alleles with rejection episodes and early graft loss (EGL) in renal transplant recipients. One hundred and eighty four HLA-DMA alleles were retrospectively analyzed by DNA sequence analysis in 92 kidney transplant recipients. The gene frequencies of HLA-DMA *0101, *0102, *0103 and *0104 were found to be similar in all recipients, regardless of rejection vs non rejection episodes and EGL incidence. In conclusion, HLA-DMA allele polymorphism did not impact renal allograft outcome.

Alleles↗

PubMed1998

Multiple epitopes of HLA-DRB1*0411 are recognized by T-cell clones originated from individuals carrying other DR4 subtypes.

HLA polymorphism dictates the binding and recognition of specific peptides, leading to variations in individual immune responses and may contribute to autoimmune disorders and outcome in organ transplantation. We have studied the molecular basis for the cellular recognition of DRB1*0411 in individuals carrying other sequence-related DR4-alleles by characterization of T-cell clones (TLC). A set of 166 TLC were raised by priming cells from DRB1*0401,0402 and DRB1*0405,0901 individuals and 52 of them recognized DRB1*0411. Five distinct patterns of T-cell allorecognition were found: DRB1*0411 alone, DRB1*0411 and 0405, DRB1*0411 and 0406, DRB1*0411 and 0407 and DRB1*0411, 0406 and 0407, depending on responder phenotypes and epitopes recognized by their T cells. A stretch of 30 amino acids on DRB1*0411 from positions 57 to 86 behaves as a functional domain and residues S57, R71, E74 and V86 seem to be crucial in forming immunogenic determinants recognized by these TLC. The knowledge of shared amino acid residues between closely related DR4 alleles, which show similar patterns of recognition by T cells could also be useful in the selection of prospective donors for clinical transplantation of solid organs or bone marrow.

Antibodies, Monoclonal↗

PubMed2006

The -56T HLA-G promoter polymorphism is not associated with pre-eclampsia/eclampsia in Australian and New Zealand women.

OBJECTIVE: Decreased HLA-G expression has been linked to a number of pregnancy disorders, including preeclampsia, and a genetic basis for HLA-G regulation has yet to be found. The aim of this study was to determine whether a C-to-T base substitution 56 base pairs (bp) upstream from the HLA-G transcription start site is associated with preeclampsia. METHODS: 277 nulliparous women consisting of 113 normotensive, 118 preeclamptic, and 46 eclamptic patients were typed for the -56T polymorphism using restriction fragment length polymorphism and allelic discrimination analysis. RESULTS: -56T allele frequencies for eclamptic, preeclamptic, and normotensive women were 0.053, 0.030, and 0.035, respectively. A chi2 test indicated that there was no significant association with the polymorphism in preeclamptic or eclamptic women with p > 0.05. CONCLUSION: The -56T HLA-G polymorphism is not associated with preeclampsia or eclampsia in our population.

Australia↗

PubMed1986

Absence of polymorphism between HLA-B27 genomic exon sequences isolated from normal donors and ankylosing spondylitis patients.

Ninety percent of individuals with ankylosing spondylitis (AS) express HLA-B27. To determine if HLA-B27 coding sequences from normal vs AS individuals show differences that might relate to the etiology of the disease, the gene coding for this allele was cloned from three different partial genomic libraries. These libraries were made with DNA from three different cell lines expressing HLA-B27: MRWC (HLA-B27, 14), obtained from an AS patient; KCA (HLA-B27, w44), obtained from a known normal individual; and MVL (HLA-B27, 27), a homozygous consanguineous cell line of unknown origin. To increase the number of clones coding for the HLA-B locus, partial libraries were made using a complete Eco RI digestion of genomic DNA in the lambda vector 607. The libraries were screened with two probes; one probe hybridizes to all HLA-A, B, C class I genes, and the other to a small subpopulation of class I genes, including the B locus. DNA from clones hybridizing with both probes was transfected into murine L cells. Cell surface expression of HLA-B27 on murine L cells was detected with a polymorphic monoclonal antibody (ME1) specific for HLA-B27, 7, 22. DNA from those clones positive for HLA-B27 by transfection was subcloned into the Xba I site of M13mp18 and the DNA sequence for exons 2 through 4 (encoding domains alpha 1, alpha 2, and alpha 3) was determined by the dideoxy technique by using synthetic oligonucleotide primers or the M13 primer. The resulting sequences show no difference between HLA-B27 alpha 1, alpha 2, alpha 3 domains from a known AS patient and a known normal individual.

Base Sequence↗

PubMed1994

Isolating fetal cells in maternal circulation for prenatal diagnosis.

Fetal cells unequivocally exist in and can be isolated from maternal blood. Erythroblasts, trophoblasts, granulocytes and lymphocytes have all been isolated by various density gradient and flow sorting techniques. Chromosomal abnormalities detected on isolated fetal cells include trisomy 21, trisomy 18, Klinefelter syndrome (47,XXY) and 47,XYY. Polymerase chain reaction (PCR) technology has enabled the detection of fetal sex, Mendelian disorders (e.g. beta-globin mutations), HLA polymorphisms, and fetal Rhesus (D) blood type. The fetal cell type that has generated the most success is the nucleated erythrocyte; however, trophoblasts, lymphocytes and granulocytes are also considered to be present in maternal blood. Fetal cells circulate in maternal blood during the first and second trimesters, and their detection is probably not affected by Rh or ABO maternal-fetal incompatibilities. Emphasis is now directed toward determining the most practical and efficacious manner for this technique to be applied to prenatal genetic diagnosis. Only upon completion of clinical evaluations could it be considered appropriate to offer this technology as an alternative to conventional invasive and non-invasive methods of prenatal cytogenetic diagnosis.

Cell Separation↗

PubMed1996

Effect of environmental factors on PCR-DNA analysis from dental pulp.

This study was designed to observe the results of DNA typing on teeth subjected to aging, different temperatures and various environmental factors. A total of 570 teeth were studied. The study included the analysis of the PCR-based polymorphisms HLA DQA1, D1S80, HUMTH01, HUMFES/FPS and the XY homologous gene amelogenin. In general the best results were obtained with the XY homologous gene amelogenin, followed by the two STRs studied (HUMTH01 and HUMFES/FPS). The small fragment sizes and the method of detection used after PCR amplification are the main factors explaining this fact. In general, teeth submerged in water gave the poorest results. Teeth exposed to outdoor conditions provided better results than teeth buried in sand or soil, but even in these cases good results were obtained. Up to 4 degree C, temperature had only a slight influence on the results. Positive results were obtained in most cases at high temperatures (400 degrees C for 2 min) which are rarely reached in practical casework. Positive typing results for the XY homologous gene amelogenin and the STRs were obtained from teeth 10-30 years old. The usefulness of dental pulp for identification purposes is exemplified in some actual cases.

DNA Fingerprinting↗