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HLA Haplotypes (hla + haplotype)
Selected AbstractsA case study of familial anti,phospholipid syndromeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2002S. Bhattacharya Summary Anti-phospholipid syndrome (APS) may have a familial association. In particular, association has been demonstrated between APS and HLA-DR 4, HLA-DR 7 and HLA-DRB1 14 alleles. Here we have described a family sharing the common haplotype of HLA-DR 7 where definite or probable anti,phospholipid syndrome has been identified in six of the seven family members. Apart from the index case, the other family members have demonstrated partial association in spite of sharing the incriminated haplotype. This could be ascribed either to variable penetrance of the involved genes or to the role of an unaccounted for environmental factor. Alternatively, it is possible that the coexistence of the HLA haplotype and the anti-phospholipid antibodies is coincidental. [source] Loss of heterozygosity on chromosome 6 in HPV-16 positive cervical carcinomas carrying the DRB1*1501-DQB1*0602 haplotypeGENES, CHROMOSOMES AND CANCER, Issue 4 2004Hugo Arias-Pulido High-risk human papillomaviruses (HPVs), specifically HPV-16 and -18, have been associated with the development of carcinoma in situ (CIS) and of invasive cervical cancer (CC). However, only a small fraction of HPV-infected women will show signs of disease progression, suggesting that other factors in the carcinogenic pathway are needed. We previously demonstrated that human leukocyte antigen (HLA) DRB1*1501-DQB1*0602 (high risk) was associated with the development of CIS and CC tumors in HPV-16-positive patients. To characterize the molecular changes that could be relevant to tumor progression, we compared the extent of loss of heterozygosity (LOH) on chromosome 6 in HPV-16-positive CIS patients who were carriers of high-risk and neutral HLA haplotypes. CIS and CC cases demonstrated similar LOH patterns. A wide range of LOH frequencies was found at 6p (10,53%) and 6q (5,28%) in CIS cases, suggesting that LOH is an early event in the carcinogenic process. A comparative analysis of LOH frequencies in the high-risk versus the neutral HLA haplotypes showed a statistically significant difference in the extent of LOH at 6p24,p25 (58.6% versus 25.8%; P = 0.018) and at 6p21.3 (79.3% versus 35.5%; P = 0.001), a region that contains the HLA complex. LOH at this region could affect genes encoding HLA class I,II molecules, as well as factors responsible for the assembly, transport, and stable expression of HLA molecules. These losses may be a reflection of both an abnormal immune response and a general genome-wide instability resulting from virus persistence. © 2004 Wiley-Liss, Inc. [source] Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in TaiwaneseINTERNATIONAL JOURNAL OF CANCER, Issue 6 2003Cheng-Chan Lu Abstract NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (,40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2+B46+ individuals are at greater risk for NPC than A2,B46, individuals in both the population studied and the ,40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2+B38+ individuals were at higher risk than A2,B38, individuals in both the population studied and the ,40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus. © 2002 Wiley-Liss, Inc. [source] MHC microsatellites in a Southern Brazilian populationINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2009C. Sens-Abuázar Summary Microsatellites are short tandem repeats of 1,6 bp DNA fragments, which are found throughout the genome. Due to their high levels of polymorphism, many of them are used as markers for population studies. Here we report an investigation on four microsatellites (D6S273, D6S2792, STR_MICA and D6S2810) located within the major histocompatibility complex in a sample of 281 Southern Brazilians of European ancestry. Allelic and haplotypic frequencies are described, as well as linkage disequilibrium (LD) between alleles of these microsatellites and alleles of three HLA genes: HLA-B, HLA-DRB1 and HLA-DQB1. The most polymorphic microsatellite was D6S2810, located close to the HLA-B locus. Strong LD was observed between alleles of microsatellites and HLA genes. The strongest associations occurred among STR_MICA*A5.1,HLA-B*13, STR_MICA*A6,HLA-B*49, STR_MICA*A9,HLA-B*39, STR_MICA*A9,HLAB*57, D6S2810*334,HLA-B*14, D6S2810*334,HLA-B*38, STR_MICA*A5.1,HLA-DRB1*1501,HLA-DQB1*0602 and D6S2810*344,HLA-DRB1*0411,HLA-DQB1*0302. This study contributes with important information on HLA haplotypes, and is potentially useful in resolving cases of low resolution HLA genotyping ambiguities. [source] HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance?INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2008E. Albanidou-Farmaki Summary The aim of this study was to investigate the genetic association between recurrent aphthous stomatitis (RAS) and human leucocyte antigen (HLA) class I and II alleles and HLA haplotypes. Families selected had at least one child suffering from recurrent aphthous stomatitis in addition to one or both of the parents. HLA-A, -B and -DR alleles were typed in 29 families, 27 nuclear and two extended (121 subjects). HLA haplotypes of all family members with RAS were compared with those who were RAS negative. Although major histocompatibility complex class I and II gene analysis failed to demonstrate any significant association between RAS and HLA antigens, the study of HLA haplotypes revealed a significant association between HLA haplotypes and susceptibility to RAS. The results indicate that susceptibility to RAS segregates in families in association with HLA haplotypes. [source] MICA and MICB microsatellite alleles in HLA extended haplotypesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2001E. Bolognesi Summary The present study is a contribution to the definition of the linkage disequilibrium relationship of MICA and MICB with adjacent loci and to the characterization of extended HLA haplotypes. These issues are of importance for the identification of disease associations and for a better definition of donor,recipient compatibility in bone-marrow grafts through the typing of haplospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage disequilibria with HLA-B and TNFa were detected in the Italian population for both MICA and MICB microsatellite alleles, in spite of the high mutability rate of the larger MICB alleles. Some strong associations were also detected between MICB and DRB1. The strongest associations (P < 0.001, D, > 0.7) were those of MICA-A4 with HLA-B18, B27 and TNFa1, MICA-A5 with HLA-B35, B61 and B62, MICA-A5.1 with HLA-B7, B8, B13, B63 and MICB-CA24, MICA-A6 with HLA-B51, MICA-A9 with HLA-B39, B57 and TNFa2, MICB-CA14 with HLA-B14, B27 and TNFa1, MICB-CA15 with HLA-B52, TNFa4 and TNFa13, MICB-CA17 with HLA-B7 and TNFa11, MICB-CA18 with HLA-B13 and TNFa7, MICB-CA22 with HLA-B57, and MICB-CA24 with HLA-B8 and TNFa2. From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid extended haplotypes. [source] HLA typing in Taiwanese patients with oral submucous fibrosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2004Hsin-Ming Chen Background:, A significant association of certain human leukocyte antigens (HLA) and haplotypic pairs with oral submucous fibrosis (OSF) has been reported. However, controversial result of no HLA association with OSF has also been reported. In this study, the phenotype and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 in 135 Taiwanese OSF patients were calculated and compared with those in 540 healthy control Taiwanese. Methods:, The analysis of HLA-A, -B, and -C antigens, and of HLA-DRB1 and -DQB1 alleles in OSF patients and healthy control subjects, was performed by serologic typing and DNA typing using polymerase chain reaction with sequence-specific primers (PCR-SSP), respectively. Results:, We found that the phenotype frequency of HLA-B76 (3.0%) in OSF patients was significantly greater than that (0%) in healthy control subjects (corrected P (Pc) = 0.000). In addition, the haplotype frequencies of HLA-B48/Cw7 (3.0%), -B51/Cw7 (6.7%), and -B62/Cw7 (8.2%) in OSF patients were significantly greater than the corresponding haplotype frequencies (0, 0.7, and 1.9%, respectively) in healthy control subjects (Pc = 0.000). The relative risk (RR) values of haplotypes B51/Cw7 (9.57) and B62/Cw7 (4.7) were greater than the RR values of phenotypes B51 (1.81), B62 (2.31), and Cw7 (1.91) in OSF patients. In addition, the etiologic fraction (EF) value of haplotype B51/Cw7 (0.63) was higher than the EF values of phenotypes B51 (0.2) and Cw7 (0.59). Conclusions:, We conclude that some Taiwanese areca quid (AQ) chewers with particular HLA phenotypes and haplotypes are prone to have OSF. In addition, some particular HLA haplotypes may play more important roles than the individual HLA phenotypes for the genetic susceptibility to OSF. However, the significantly increased HLA phenotype B76 and three of the common HLA haplotypes detected are present in only about 20% of incident cases of OSF. [source] AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECEDCLINICAL ENDOCRINOLOGY, Issue 5 2010Sara Cervato Summary Objective, To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ- or non-organ-specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison's disease (AD) or chronic candidiasis (CC). Design, Patients and Measurements, Twenty-four patients who had CH without AD or CC were included in the study. AIRE gene mutations in all 14 exons were studied using PCR in 24 patients, 105 healthy controls and 15 first-degree relatives of CH patients with AIRE mutations. Human leucocyte antigens (HLA) were determined for all 24 patients and 105 healthy controls. Autoantibodies to a range of antigens including NACHT leucine-rich-repeat protein-5 (NALP5) and interferon omega (IFN,) were tested in all 24 patients. Results, AIRE gene mutations were found in 6 of 24 (25%) patients, all females, and this was significantly higher (P < 0·001) compared with AIRE mutations found in healthy controls (2/105). Three patients (12·5%) had homozygous AIRE mutations characteristic of Autoimmune-Poly-Endocrinopathy-Candidiasis-Ectodermal-Dystrophy and all three were also positive for IFN,-autoantibodies. Three patients (12·5%) had heterozygous AIRE mutations; two of these were novel mutations. One of the patients with heterozygous AIRE mutations was positive for both NACHT leucine,rich-repeat protein 5 and IFN, autoantibodies. Heterozygous AIRE mutations were found in 10 of 15 first-degree relatives of CH patients with AIRE mutations, although none was affected by CH. Class II HLA haplotypes were not statistically different in patients with CH compared to healthy controls. Conclusions, Analysis of AIRE gene mutations together with serum autoantibody profile should be helpful in the assessment of patients with CH, in particular young women with associated autoimmune diseases. [source] | ||||||||||