SEARCH · PubMed Health

Results for “HLA polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources

PubMed2003

HLA class I variation in the West African Pygmies and their genetic relationship with other African populations.

We have studied the polymorphism of HLA class I in two West African Pygmy populations, namely, the Bakola from Cameroon and the Mbenzele from the Central African Republic. A unique number of HLA alleles and haplotypes showed specific patterns of these populations. In this study, we identify two alleles (B*37, B*41) and three haplotypes (A*30-B*37, A*66-B*41 and A*68-B*58) that appear to be 'private' or typical of Western Pygmies. These data reflect similarities with the AKA Pygmies from the Central African Republic. On the other hand, we failed to identify alleles that are found at high frequencies among other sub-Saharan populations (B*42, B*51). Allelic and haplotypic frequency distributions show differences between the two Pygmy groups, e.g. B*35 was very common in the Mbenzele but has been found to be absent in the Bakola. In contrast, B*53, which is found in the Bakola, has been found to be rare in the Mbenzele Pygmies. In order to analyse the genetic relationships of the Bakola and Mbenzele Pygmies with other sub-Saharan populations, HLA gene frequencies were subjected to the Neighbour-Joining tree analysis. The Mbenzele, Bakola and AKA were found to be relatively close to each other and isolated from other sub-African populations. However, both the genetic distances and the within-group variation suggests that the Bakola are more admixed with Bantu farmers than Mbenzele.

Africa, Western↗

PubMed2000

Independent contribution of HLA-DRB1 and TNF alpha promoter polymorphisms to the susceptibility to Crohn's disease.

Although a number of studies reported the association of HLA-DRB1 and Crohn's disease (CD), the actual alleles associated with CD are considerably variable among populations. On the other hand, the relevance of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of CD is established through experimental as well as clinical studies, raising the possibility that TNFA polymorphism is primarily or independently contribute to the association of HLA region genes with CD. New polymorphisms which may affect the transcriptional activity were recently reported within the upstream promoter region of TNFA gene. In the present study, we compared HLA-DRB1, TNFA promoter and TNF receptor 2 (TNFR2) genotypes in 154 Japanese patients with CD and 265 unrelated healthy controls to evaluate the individual contribution of these genes to the genetic predisposition to CD. Significant positive association was observed in HLA-DRB1*0405 (P = 0.001, odds ratio (OR) = 2.02) and 0410 (P = 0.002, OR = 4.79). Among the TNFA promoter haplotypes, TNFA-U03 (-1031C, -863A, -857C) was significantly increased (P = 0.008, OR = 1.64), while TNFA-U04 (-1031C, -863C, -857C) was significantly decreased (P = 0.014, OR = 0.12), in CD. The association with TNFA-U03 was independent of that with DRB1*0405 and 0410, and apparent additive or multiplicative effect was not observed between these susceptibility alleles. No association was observed between TNFR2-196M/R polymorphism and CD. These results indicated that both of HLA-DRB1 and TNFA promoter polymorphisms contribute to the susceptibility to CD in an independent manner.

Adult↗

PubMed1994

Association of TAP2 polymorphism with rheumatoid arthritis is secondary to allelic association with HLA-DRB1.

OBJECTIVE: To study polymorphisms of the newly described TAP2 locus in rheumatoid arthritis (RA) and to analyze their relationship with HLA-DRB1 alleles previously implicated in the development of the disease. METHODS: TAP2 polymorphic residues at 3 sites, Val/Ile-379, Ala/Thr-565, and Ala/Thr-665, were characterized by amplification refractory mutation system polymerase chain reaction in 185 RA patients and 48 HLA-DR4 positive healthy controls. HLA-DR4 subtypes were determined by sequence-specific priming and oligonucleotide hybridization. RESULTS: The frequencies of Ile-379, Thr-565, and Thr-665 were significantly increased in DR4 positive versus DR4 negative RA patients. TAP2 genotype distributions also differed between the patient groups stratified by DR4 status. However, no significant differences in TAP2 polymorphisms were observed between DR4 positive RA patients and DR4 positive controls, although relationships between specific DR4 subtypes and TAP2 variants were identified. CONCLUSION: Particular TAP2 polymorphisms are associated with distinct HLA-DR specificities in both normal and RA populations. Thus, the prevalence of specific TAP2 residues and genotypes in RA appears to be secondary to the HLA-DR frequencies and genotypic combinations that are typical of RA.

Adult↗

PubMed1997

HLA-DR and -DQB1 DNA polymorphisms in a Vietnamese Kinh population from Hanoi.

We report here the DNA polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) typing of the HLA-DR B1, B3, B4, B5 and DQB1 loci for a sample of 103 Vietnamese Kinh from Hanoi, and compare their allele and haplotype frequencies to other East Asiatic and Oceanian populations studied during the 11th and 12th International HLA Workshops. The Kinh exhibit some very high-frequency alleles both at DRB1 (1202, which has been confirmed by DNA sequencing, and 0901) and DQB1 (0301, 03032, 0501) loci, which make them one of the most homogeneous population tested so far for HLA class II in East Asia. Three haplotypes account for almost 50% of the total haplotype frequencies in the Vietnamese. The most frequent haplotype is HLA-DRB1*1202-DRB3*0301-DQB1*0301 (28%), which is also predominant in Southern Chinese, Micronesians and Javanese. On the other hand, DRB1*1201 (frequent in the Pacific) is virtually absent in the Vietnamese. The second most frequent haplotype is DRB1*0901-DRB4*01011-DQB1*03032 (14%), which is also commonly observed in Chinese populations from different origins, but with a different accessory chain (DRB4*0301) in most ethnic groups. Genetic distances computed for a set of Asiatic and Oceanian populations tested for DRB1 and DQB1 and their significance indicate that the Vietnamese are close to the Thai, and to the Chinese from different locations. These results, which are in agreement with archaeological and linguistic evidence, contribute to a better understanding of the origin of the Vietnamese population, which has until now not been clear.

Alleles↗

PubMed2003

Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms.

Hepatic lipase activity (HLA) is a determinant of HDL levels, and a polymorphism in the hepatic lipase gene (LIPC) promoter (C-514T) has been hypothesized to account for higher HDL in blacks and Japanese compared with whites. To determine whether the polymorphism contributes to ethnic differences in HDL, we compared LIPC allele frequencies and HLA in Japanese American (JA; n = 84), black American (BA; n = 94), and white American (WA; n = 110) men and women. The LIPC polymorphism was associated with HLA in all cohorts (BA, P = 0.012; JA, P = 0.008; WA, P = 0.009). WA men had 49% and 58% higher HLA than BA and JA men, respectively (both P < 0.05), yet no differences in HLA were found between the women. The higher HLA in the WA men remained after adjustment for the LIPC polymorphism's effect on HLA (P = 0.037) but was erased after adjustment for waist-to-hip-ratio (P = 0.46). Although the WA men had lower HDL and HDL(3) than the JA and BA men (all P < 0.05), there were no differences in HDL(2), implying that variance in HLA may not underlie the ethnic differences in HDL levels. These results suggest that 1) the LIPC promoter polymorphism contributes to variation in HLA and HDL(2) in the three ethnic groups; 2) WA men had higher HLA than BA and JA men, related to ethnic differences in central adiposity but not LIPC allele frequency; and 3) the higher HLA in WA men did not contribute to the ethnic differences in HDL, as the differences in HDL were made up entirely of differences in HDL(3) and not HDL(2).

Asian People↗

PubMed2005

Genetic variants in nonclassical major histocompatibility complex class I human leukocyte antigen (HLA)-E and HLA-G molecules are associated with susceptibility to heterosexual acquisition of HIV-1.

Human leukocyte antigen (HLA)-E and HLA-G molecules act as powerful modulators of the innate immune response. The present study shows that the HLA-E(G) genetic variant (the HLA-E*0103 allele) alone is significantly (P = .001) associated with a 4.0-fold decreased risk of human immunodeficiency virus 1 (HIV-1) infection in Zimbabwean women. Furthermore, women carrying the combination of the protective HLA-E(G) homozygote and HLA-G*0105N heterozygote genotypes had a 12.5-fold decreased risk of HIV-1 infection (P = .03), compared with women carrying neither genotype. These associations remained significant after adjustment was made for other significant sociodemographic risk factors for HIV prevalence in this population. In conclusion, HLA-E and HLA-G polymorphisms can independently and synergistically influence susceptibility to heterosexual acquisition of HIV-1.

Female↗

PubMed1991

HLA-DR and DQ DNA genotyping in multiple sclerosis patients in Northern Ireland.

DNA from multiple sclerosis (MS) patients and healthy control individuals from the Northern Ireland population, was assessed by restriction fragment length polymorphism (RFLP) analysis to look for disease-associated polymorphisms. HLA-DR and -DQ allogenotyping was performed using a single enzyme (TaqI)/Multiple probe system. The TaqI/DR beta RFLPs correlate well with serologically defined specificities and in addition detect further subtypes of these associated with DQ or Dw specificities. The results confirm an association of MS with DR beta 15 and show a decreased frequency of DR beta 4 in the patients. An increased frequency of DR beta 17 in patients negative for DR beta 15 was also found. There is a decrease in the frequency of the TaqI/DQ beta 3 (TA10 + ve) RFLP and the TaqI/DQ alpha 2LL genotype in the MS patients, these not being associated with DR beta 15. In addition RFLP analysis of the DPA1 and DPB1 genes reveals an MspI/DP beta 3.0-kb fragment which occurs at a higher frequency in the patients than in the controls.

Gene Frequency↗

PubMed1985

Origin of immature teratoma of the ovary.

Six cases of immature teratoma of the ovary were karyotyped and analyzed for chromosomal heteromorphisms, enzyme polymorphisms, and HLA specificities to determine their mechanism of origin. Three cases were chromosomally abnormal, with karyotypes of 48,XX, +14, +21; 47,XX, +20; and 47,XXX, respectively. The tumors with 48,XX, +14, +21 and 47,XX, +20 karyotypes were heterozygous for chromosomal heteromorphisms which were identical to those of their host and therefore originated from a premeiotic cell or failure of meiosis I. Both had a poor prognosis. The 47,XXX tumor and the three cases with normal karyotypes were homozygous for chromosome heteromorphisms and either homozygous or heterozygous for enzyme and HLA markers and therefore originated from a failure of meiosis II or duplication of a mature haploid ovum. All four had an uneventful postoperative course. These observations show that immature teratomas are like cystic teratomas in having at least three separate mechanisms of origin. However, they are unlike cystic teratomas in having a high proportion with chromosome abnormalities and a high rate of malignant transformation.

Adult↗

PubMed1997

Complementary strand analysis: a new approach for allelic separation in complex polyallelic genetic systems.

We describe a method, complementary strand analysis (CSA), for separating alleles potentially from any heterozygous genetic locus. Locus specific PCR is performed generating two allelic products. The antisense strands are isolated and hybridised with a sense reference strand to form a chimeric DNA duplex for each allele which is then separated by non-denaturing PAGE. We demonstrate the application of CSA for separation of highly polymorphic HLA-A, -B and -Cw alleles and characterisation of HLA identity in related bone marrow donors and patients. CSA is capable of resolving one nucleotide differences in a DNA fragment nearly as large as a kilobase in length.

Alleles↗

PubMed1988

Allospecific DR gene expression on the human thyroid cell.

Human thyroid epithelial cells, stimulated with recombinant gamma interferon (IF) (100 U/ml), were HLA-DR typed by means of antibody-dependent, complement-mediated cytotoxicity. The thyroid cell lysis reaction patterns were found to be similar to those obtained with autologous peripheral B cells in four of five separate experiments. Since the cytotoxic reactions with thyroid cells were sometimes incomplete with many antisera, a two-color fluorescence technique was developed to measure the specificity of the antibody-dependent, complement-mediated lysis. Using constitutively HLA-D antigen-positive Raji B lymphoblastoid cells as controls, we showed that non-polymorphic HLA-D and HLA-DR determinants could be detected on the thyroid cell surfaces by this cell lysis approach. In addition, gamma IF stimulated thyroid cells from a DR3 positive individual were lysed to a significantly greater than unstimulated autologous thyroid cells with the use of a specific monoclonal antibody to HLA-DR3, thus confirming the original HLA typing studies. These data demonstrate, for the first time, that the expression of HLA-DR antigen on the surface of human thyroid cells is allospecific and may, therefore, play an important role in the immunopathology of autoimmune thyroid disease.

Cytotoxicity, Immunologic↗

PubMed1991

Description of a polymorphism in the regulatory region of the HLA-DRA gene.

It was previously reported that the cell membrane expression of HLA class II molecules is tissue specific and variable among individuals. This variation could be explained at the level of gene regulation. Due to the fact that a coordinate regulation of the HLA-DR genes seems to exist, we focused on the HLA-DRA monomorphic gene. In order to study the polymorphism of the HLA-DRA gene regulatory region, we used restriction fragment length polymorphism analysis of polymerase chain reaction (PCR)-amplified genomic DNA. The DdeI and PvuII digestions of the amplified DNA permitted the definition of the two alleles according to the absence (allele A) or the presence (allele B) of the two polymorphic restriction sites. The presence of these sites was confirmed by direct sequencing after PCR. Using homozygous typing cells, a close relationship between the HLA-DRB coding region and the HLA-DRA regulatory region polymorphisms was shown. Furthermore, a linkage between the HLA-DRA regulatory region and DRB3 gene coding region polymorphisms could be established. These results suggested a structural argument for different levels of HLA class II genes and, consequently, of cell-surface expression of class II antigens according to the allelic specificities of DRA, DRB1, and DRB3.

Alleles↗

PubMed2004

Lack of a strong association between HLA class II, tumour necrosis factor and transporter associated with antigen processing gene polymorphisms and virological response to alpha-interferon treatment in patients with chronic hepatitis C.

The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response to alpha-interferon in patients with chronic hepatitis C. Twenty-seven sustained responders and 55 non-responders to alpha-interferon monotherapy were investigated. HLA-DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR-based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (Pc). Viral genotype 1b was more frequent in responders than in non-responders (56% vs. 26%, P = 0.009). HLA-DQB1*02 occurred less frequently in responders than in non-responders (14.8% vs. 29%, Pc not significant). HLA-DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non-responders, respectively (Pc not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty-four (88.8%) responder patients as compared with 34 (61.8%) non-responders were TAP1*0101 homozygous (Pc not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment.

ATP-Binding Cassette Transporters↗

PubMed1987

RFLP of the HLA-DQ alpha region: a diallelic DX alpha polymorphism, not linked to DR and DQ specificities.

HLA-DQ alpha DNA polymorphism was studied by Southern blot analysis in a panel of 117 individuals, consisting of 56 randomly selected and 61 HLA-DR homozygous individuals. Hybridizing fragments representing DQ alpha genes correlate with DR specificities owing to linkage disequilibrium between DQ and DR. Two fragments representing DX alpha genes were identified with the restriction enzymes PvuII and TaqI and a DQ alpha cDNA probe. The two fragments of PvuII-DQ alpha hybridization (a 7200 and a 7000 basepair fragment) and the two of TaqI-DQ alpha (2200 and 1900 basepairs) have an identical distribution in the panel, and reveal gene frequencies of 49.1% and 50.9%; they behave as alleles of the putative DX alpha locus. The panel study shows that the DX alpha fragments are not linked with the DR or DQ specificities but segregate along with HLA as shown in family studies.

Alleles↗

PubMed2006

The association between multidrug resistance-1 gene polymorphisms and outcomes of allogeneic HLA-identical stem cell transplantation.

The impact of single nucleotide polymorphisms of two loci (C3435T and G2677T/A) of the multidrug resistance-1 gene (MDR1) was investigated in 82 patients undergoing allogeneic stem cell transplantation (SCT). The GG genotype on G2677T/A loci was associated with higher non-relapse mortality than was the non-GG genotype (67% vs. 32%, p=0.0073), but not the C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival was significantly correlated with the G2677T/A genotype (p=0.0048). Multivariate analysis also showed that the GG genotype at G2677T/A had an unfavorable prognosis in terms of overall survival (p=0.003) and non-relapse mortality (p=0.031). In conclusion, the G2677T/A genotype seems to be associated with transplantation outcomes, especially non-relapse mortality.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Associations between human leukocyte antigens and nonresponsiveness to influenza vaccine.

Influenza remains a major cause of morbidity and mortality, particularly in at-risk groups where vaccination reduces complications of infection but is not universally protective. In order to determine whether human leukocyte antigen (HLA) class II polymorphisms modulate anti-influenza antibody responses to vaccination, a cohort of HLA-typed at-risk donors was investigated. The subjects were recruited from a single urban family practice. Hemagglutination-inhibition (HAI) titers were measured immediately before and 28 days after subunit vaccination. Nonresponsiveness was defined as failure to mount an HAI response to any component of the trivalent influenza vaccine. When the nonresponders and responders with HLA class II were compared, the nonresponder group had more HLA-DRB1*07-positive donors (13/32 vs. 6/41 responders; P=.016, Fisher's exact test) and fewer HLA-DQB1*0603-9/14-positive donors (2/32 vs. 14/41 responders; P=.0045). Thus, polymorphisms in HLA class II molecules appear to modulate antibody responses to influenza vaccination.

Adult↗

PubMed2007

Genetic link between Chaoshan and other Chinese Han populations: Evidence from HLA-A and HLA-B allele frequency distribution.

The genetic polymorphism of HLA-A and HLA-B loci was investigated in 505 Chaoshanese using PCR-SSP method. Among the HLA-A alleles detected, A*11 (35.64%) was most frequent, followed by A*02 (31.78%). Of 34 HLA-B alleles tested, 30 were observed, in which B*60 (21.68%), B*46 (14.46%), and B*58 (10.69%) were highly predominant. Comparison was made with other nine Chinese Han ethnic groups covering the Mainland China, Taiwan, Hong Kong, and Singapore. The high frequent alleles found in Chaoshanese were also common in other Chinese groups compared though the frequency levels varied from group to group. The phylogenic tree analysis based on the HLA-A and -B allele frequencies of all the 10 Chinese ethnic groups revealed that Chaoshanese, while clustering in general with the southern China-related Han Chinese, had the highest affinity to the Mainland Minnanese, but separated distinctively from the northern Han Chinese. The study, however, was yet to confirm the hypothesis of the Central Plains Han origin of Chaoshanese. Interestingly, the alleles (B*46, B*38, and B*58) and the related haplotypes (A*02-B*46 and A*33-B*58) that are positively associated with nasopharyngeal carcinoma (NPC), a disease prevailing predominantly among southern Chinese, were always at much higher frequencies among southern Chinese than among northern Chinese, whereas A*31 and B*13, the two alleles with highly protective effects for NPC, and the associated haplotype A*30-B*13 were predominantly high in northern Chinese. The different genetic background between northern and southern China may explain, at least partially, the prevalence of NPC among southern Chinese.

Asian People↗

PubMed1987

Monomorphic anti-HLA monoclonal antibody (W6/32) recognizes polymorphic H-2 heavy-chain determinants exposed by association with bovine or human but not murine beta 2-microglobulin.

W6/32 is a mouse anti-HLA class I monoclonal antibody (MoAb) of BALB/c (H-2d) origin with a monomorphic reaction pattern on human cells. In this study, we explain that the previously reported (Ivanyi D et al., Immunogenetics 20:6gg, 1984) cross-reactions of W6/32 with the H-2Db antigen are completely dependent on the formation of a complex between the H-2Db heavy chain with bovine beta 2-microglobulin (beta 2m) from the culture medium. M0Ab W6/32 cross-reacted with various H-2 class I antigens only in the presence of bovine or human beta 2m but not in the presence of beta 2m from other species (goat, sheep, rabbit) or syngeneic mouse beta 2m. The exposure of the W6/32 determinant on mouse cells was dependent on the concentration of human or bovine beta 2m and was influenced by the temperature and time of incubation. The reaction pattern of W6/32 on a large panel of mouse strains showed that the binding is due to at least two critical factors: (i) the H-2 haplotype of the target cells; and (ii) the substitution of murine beta 2m for bovine or human beta 2m. These results show that exposure of a polymorphic class I determinant is dependent on the species origin of beta 2m with which the heavy chain is complexed. Comparison of beta 2m amino acid sequences from various species does not give a clear answer about the shared quality of human and bovine beta 2m. One amino acid position (89) was identified at which human and bovine beta 2m are identical but differ from all other known beta 2m sequences.

Animals↗

PubMed1991

HLA-DR and the 5' insulin gene polymorphism in insulin-dependent diabetes.

While the human leukocyte antigen (HLA) region provides the major susceptibility for insulin-dependent (type I) diabetes mellitus (IDDM), other (non-HLA) genes must also play a role. Population studies have shown an increased frequency of small insertions (class I alleles) 5' to the insulin gene in individuals with IDDM, suggesting that this region may account for part, if not all, of the non-HLA genetic predisposition. However, no data are available as to whether the relation of the insulin gene polymorphism is to a DR-defined subset of IDDM or with all of IDDM. To test the hypothesis that specific combinations of HLA and insulin gene polymorphism alleles may interact in providing susceptibility for IDDM, HLA-DR and 5' insulin gene insertion size have been determined in 300 individuals with IDDM. The frequency of class 1 insulin gene alleles in the entire sample is 0.79 and the frequency of class 3 alleles (large inserts) is 0.20. The frequencies of class 1 alleles were equal across all DR classes: 0.79 in the DR3/X IDDM subjects, 0.80 in the DR4/X, 0.79 in the DR3/4, and 0.78 in those with DRX/X. Additionally, the frequencies of class 1/1 homozygotes and 1/3 heterozygotes were similar between HLA-DR types. These results suggest that the HLA region and the region 5' to the insulin gene provide independent and nonsynergistic genetic risks for IDDM.

Diabetes Mellitus, Type 1↗