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At least 703 records · Page 39Linked to original sources
PubMed2003

The HLA-DRB, -DQB polymorphism and anti-insulin antibody response in Slovenian patients with type 1 diabetes.

A combination of specific HLA class II antigens and the presence of type 1 diabetes (T1D)-related antibodies has a high positive predictive value for T1D but low sensitivity. The aim of the present study was to determine the frequencies of HLA-DRB-DQB deduced haplotypes associated with susceptibility and protection in Slovenian patients with established T1D, to evaluate the relationship between the HLA-DRB1-QBP-DQB1 haplotypes and the presence of insulin autoantibodies (IAA) and glutamic acid decarboxylase antibodies (GADA), and to access the possible impact of polymorphic QBP promoters on this relationship. A cohort of 135 patients with T1D (age 17.5 +/- 7.0 years, duration of T1D 9.14 +/- 6.3 years) was investigated. HLA-DRB1 and DQB1 alleles were typed using the polymerase chain reaction (PCR)-reverse line blot method. QBP promoter region alleles were determined using PCR-sequence-specific oligonucleotide hybridization (SSO) and PCR-sequence-specific primers (SSP). IAA and GADA antibodies were determined by enzyme-linked immunosorbent assay (ELISA). The chi-square test with Yates' correction was used for statistical analysis. Deduced haplotypes DRB1*0301-DQB1*0201 (P = 0.0001, OR = 3.4), DRB1*0401-DQB1*0302 (P = 0.0001, OR = 29.8), and DRB1*0402-DQB1*0302 (P = 0.008, OR = 4.7) were significantly more common, and DRB1*1501-DQB1*0602 (P = 0.0001, OR = 0.03) significantly less common in the investigated cohort than in a Slovenian control group. The highest risk and the strongest protective HLA-DR-DQ haplotypes found in Slovenian patients with T1D did not differ from those found in other Caucasian populations. While the DRB1*0301-QBP2.1-DQB1*0201 haplotype, where QBP2.1 did not help to further distinguish DQB1*0201-possessing haplotypes in IAA-positive and IAA-negative patients, was strongly associated with the presence of IAA, the DRB1*0101-QBP5.12-DQB1*0501 haplotype, although not protective compared to the control population, was associated with an absence of IAA in the investigated cohort. It is suggested that there may be a combined influence of the QBP5.12 promoter and the DQB1*0501 functional molecule on reduced IAA production.

Adolescent↗
PubMed1994

HLA class II polymorphism in Thai insulin-dependent diabetes mellitus.

Fifty-seven Thai IDDM patients were studied for HLA class I by LCT and HLA class II by LCT and PCR-RFLP. It was found that DRB1*0301, DR3, DQB1*0201, DRB3*0202, DQA1*0501 and DQ2 were significantly increased with R.R. = 10.0, 6.6, 4.2, 3.7, 3.5 and 3.2 and Pc < 0.005, 0.001, 0.01, 0.005, 0.01 and 0.005, respectively. In contrast, DQA1*0101, DRB3*0301, DR5 and DQ1 were significantly decreased with R.R. = 0.2, 0.2, 0.3 and 0.5 and Pc < 0.01, 0.05, 0.01 and 0.05, respectively. The primary factor for IDDM susceptibility is probably DRB1. The homozygous Asp57/Asp57 DQB1 genotype appears to determine resistance to IDDM while Arg52-DQA1, non-Asp57-DQB1 haplotype confers susceptibility to IDDM. The common haplotypes in Thai IDDM cases were DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201, DPB1*0401 and DRB1*0405, DQA1*0301, DQB1*0402 (or 0401 or 0302), DPB1*0401 (or 0301 or 1501). The less common haplotypes were DRB1*0406, DQA1*0301, DPB1*0302, DPB1*0501 and DRB1*1202, DRB1*0301, DQA1*0601, DQB1*0301, DPB1*0501. DR3 was increased in both gender groups with early onset (< 10 years) regardless of a family history of DM. However, DR3/DR4 genotype was increased only in female patients with a family history of DM and early onset. In conclusion, DRB1, DRB3, DQA1 and DQB1, but not DPB1 are involved in the occurrence of IDDM. The cooperation of HLA class II and X-chromosome may contribute to the development of IDDM in addition to other factors such as other genetic (chromosomes 11, 19, 14, 7), immunologic and environmental factors which require further study.

Adolescent↗
PubMed2002

HLA class I polymorphism in a Moroccan population from Casablanca.

We have studied the distribution of HLA-A and -B alleles and haplotypes by sequence-specific primer amplification in a sample of 100 unrelated healthy individuals belonging to both Berber and Arabic-speaking groups from the region of Casablanca in Morocco. Among the 17 HLA-A and 23 HLA-B alleles observed, the most frequent were HLA-A2 (21%), -A1 (11%), -A3 (10%), -B44 (11.4%), -B50 (9.9%), -B5(8.5%) and -B35 (6.5%). Six two-locus haplotypes were observed with a frequency above 5%: A2-B50 (9.6%), A23-B44 (7.4%), A2-B15 (6.4%), A68-B39 (5.3%), A1-B51 (5.3%) and A68-B44 (4.3%). Our data confirm that, on the basis of genetic distances, the majority of present-day North Africans from Morocco are closely related to Berbers and also to Iberians. They cluster apart from Middle-Eastern Mediterranean populations, and show greater genetic distances to Eastern and other Mediterranean populations. This study will serve as a reference for further anthropological studies, as well as studies of HLA and disease associations.

Evolution, Molecular↗
PubMed2004

TNF-alpha promoter polymorphisms and extended HLA and TNF-alpha haplotypes in Koreans based on 100 families.

We investigated five single-nucleotide polymorphism (SNP) sites of tumor necrosis factor-alpha (TNF-alpha) promoter, the distribution of five-locus TNF-alpha haplotypes, and extended human leukocyte antigen (HLA)/TNF-alpha haplotypes in 200 parents from 100 unrelated Korean families. TNF-alpha SNPs were typed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and PCR restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of -1031C, -863A, -857T, -308A, and -238A alleles were 0.185, 0.145, 0.140, 0.060, and 0.040, respectively. The allele frequencies in Koreans were similar to those of Japanese. A total of five TNF-alpha haplotypes (-1031/-863/-857/-308/-238) were detected in 196 parents: TCCGG (frequency 0.617), CACGG (0.143), TCTGG (0.143), TCCAG (0.061), and CCCGA (0.036). Five most common extended HLA/TNF-alpha haplotypes (frequencies >0.020) accounted for 16% (63/392) of the total haplotypes. A total of 223 HLA haplotypes and 239 HLA/TNF-alpha haplotypes were detected, indicating that most HLA haplotypes are exclusively associated with particular TNF-alpha haplotypes.

Family↗
PubMed1993

Restriction fragment length polymorphism of HLA-DQ and -DR allogenotypes in normal southern Chinese.

We have examined the Taq I restriction fragment length polymorphism (RFLP) of the MHC class II regions of 96 normal Southern Chinese with respect to the HLA-DRB, -DQA, and -DQB genes. The data were compared with the DR and DQ serotyping. RFLP correlates well with the serological typing of the DR types of Chinese. Variants are seen in DR2 and DR12. The variant in DR12 with a 10 kb at the upper band (DR12b) is not found in Caucasoids and is more frequent in Chinese (19.4% of the alleles). With the help of DQA and DQB RFLP the assignment of genotyping of DRB types is facilitated. Some of the linkage disequilibrium patterns among DRB, DQA and DQB are different from Caucasoids. This is particularly obvious in the DR2 and DR5 haplotypes. In the 96 Southern Chinese, the 3 commonest haplotype frequencies are: DR12b, DQ alpha 1b, DQ beta 3b (18.3%); DR9, DQ alpha 3, DQ beta 3a (15.7%); DR4, DQ alpha 3, DQ beta 3a (14.2%). The various DR beta, DQ alpha. DQ beta genes can be accurately defined in Chinese by RFLP. Polymerase chain reactions using sequence-specific primers were performed to confirm the various HLA-DRB and -DQB alleles. The use of RFLP is important in the study of HLA matching and HLA-disease association in Southern Chinese.

Asian People↗
PubMed1993

Polymorphism in the promoter region of HLA-DRB genes.

Polymorphism is a hallmark of the molecules encoded within the MHC of humans and other mammals. Recently, evidence of polymorphism has also been shown to exist in the transcriptional regulatory regions of HLA-DQB genes. In this article, we report that polymorphism exists also in the promoter region of HLA-DRB genes. The sequence of the regulatory region of DRB genes from five homozygous DR B-cell lines, each of a distinct DR haplotype, revealed a number of differences, some of which are in the critical class II boxes that are generally conserved in class II promoters. The major differences occurred in a comparison of DR4 to the other DR haplotypes. These data suggest the existence of another important source of HLA class II polymorphism that may play a role in susceptibility to HLA-associated autoimmune disease.

Base Sequence↗
PubMed1988

Nature of polymorphism in HLA-A, -B, and -C molecules.

Diversity in 39 HLA-A, -B, and -C molecules is derived from 20 amino acid positions of high variability and 71 positions of low variability. Variation in the structurally homologous alpha 1 and alpha 2 domains is distinct and may correlate with partial segregation of peptide and T-cell receptor binding functions. Comparison of 15 HLA-A with 20 HLA-B molecules reveals considerable locus-specific character, due primarily to differences at polymorphic residues. The results indicate that genetic exchange between alleles of the same locus has been a more important mechanism in the generation of HLA-A, -B, and -C diversity than genetic exchange events between alleles of different loci.

Amino Acid Sequence↗
PubMed1999

[Analysis of HLA-DRB1 allele polymorphism for patients with allergic rhinitis].

OBJECTIVE: To analyze the association between allergic rhinitis and HLA-DRB1 in northeast area of China. METHODS: Using polymerase chain reaction/sequence specific primers (PCR/SSP) technique, we studied distributive speciality of HLA-DRB1 alleles in 35 patients with (AR) and 94 healthy controls. RESULTS: The statistical results showed that the frequencies of DRB1 * 0101.2 and DRB1 * 0302 alleles were significantly higher in AR patients than in those of controls. The frequencies of DRB1 * 0101,2 and DRB1 * 0302 were 12.86% (relative risk = 15.92 Pc < 0.0004) and 5.71% (relative risk = 12.00, Pc < 0.05) respectively, the other gene frequencies bore no significant difference. CONCLUSION: AR was associated with HLA-DRB1 * 0101.2 and DRB1 * 0302 alleles.

Adult↗
PubMed1998

MICA gene polymorphisms and HLA-B27 subtypes in Japanese patients with HLA-B27-associated acute anterior uveitis.

PURPOSE: HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) seems to be triggered by external factors in persons with a particular genetic background. It is still uncertain whether HLA-B27 or other gene(s) near the HLA-B region predisposes to uveitis in a linkage disequilibrium with B27. The authors investigated microsatellite polymorphism within the transmembrane region of the MICA gene, located 47 kb centromeric of the HLA-B gene, and HLA-B27 subtypes. METHODS: Seventeen HLA-B27-positive Japanese patients with HLA-B27 AAU, 51 Japanese controls, and 20 B27-positive Japanese controls were examined for MICA gene polymorphism within the transmembrane region using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. Furthermore, B27-positive patients with HLA-B27 AAU and B27-positive controls were examined for HLA-B27 subtypes by the PCR-sequence-specific primer method. RESULTS: The microsatellite allele in the MICA gene, consisting of four repetitions of GCT/AGC (designated A4 allele), was present at a significantly higher phenotype frequency in the patient group (64.7%) than in the control group (25.5%) (chi 2 = 6.95, Pc = 0.042). Furthermore, the frequency of the A4 allele was significantly higher, even when compared with 20% in the B27-positive control group (chi 2 = 5.88, Pc = 0.042). The frequency of HLA-B27 subtypes was not significantly different between B27-positive patients with HLA-B27 AAU and B27-positive controls. CONCLUSIONS: These results suggest that the MICA gene itself, or other nearby gene(s), linked to the MICA A4 allele may be involved in the development of HLA-B27 AAU and that HLA-B27 subtypes are not important in the development of HLA-B27 AAU in a Japanese population.

Acute Disease↗
PubMed2005

[Determination of HLA-DRB1 gene polymorphism in Luoba ethnic group of Tibet].

OBJECTIVE: To investigate the frequencies of allele and genotype of HLA-DRB1 gene in Luoba ethnic group. METHODS: HLA-DRB1 genes from 92 individuals of Luoba ethnic group in Tibet Autonomous region were investigated, using PCR-SSO (polymerase chain reaction -sequence specific oligo-nucleotide) genotyping methods. We compared allele frequencies of Luoba population in HLA-DRB1 locus with that of various ethnic groups distributed worldwide, constructed the phylogenetic tree by UPGMA (unweighted pair group method with arithmetic mean), and counted genetic distance by Nei measure. RESULTS: Of the 11 DRB1 alleles detected, the two most common genes were DRBI * 04( gene frequency: 27.20% ) and DRB * 12 (25.50%) , which covered 52.70% of the total alleles detected from Luoba ethnic group. The frequencies of HLA-DRB1 * 14(15.20% ), DRB1 * 15(9.80% ) and DRB1 * 08(8.20% ) were more than 5%. Luoba was unique in the distribution of HLA alleles. The genetic distance between Luoba and Tibetan was closer than that with other population. A dendrogram based on the DRB1 genes by cluster analysis suggested that Luoba ethnic group might cluster with Tibetan firstly, then cluster with other population living in China (except Uygr) , and cluster with Caucasian and Black finally. CONCLUSION: The HLA-DRBI gene frequency of Luoba individuals in Tibet Linzhi had some differences compared with that of other Chinese population. The kindred relation between Luoba and Tibetan was closer than that with other population, which was coincident with the results of ethnology, history and sociology.

China↗
PubMed1986

Polymorphism of HLA-DR beta chains in DR4, -7, and -9 haplotypes: implications for the mechanisms of allelic variation.

We have isolated and sequenced cDNA clones corresponding to the DR beta 1 and DR beta 2 loci from two homozygous B-cell lines typed as DR7 (Burkhart) and DR9 (ISK). These nucleotide sequences were compared to beta 1 and beta 2 chains of other DR haplotypes. The first-domain sequences of beta 2 chains are identical in DR4 and DR7 haplotypes. In addition, there is strong sequence homology within the 3' untranslated regions of beta 1 genes from DR4, -7, and -9 haplotypes, thus confirming the close evolutionary relationship among these three haplotypes. In contrast, the first-domain sequences of beta 1 molecules from these haplotypes are very different from each other and do not reflect the DR4, -7, -9 family relationship. Two explanations for the differences in degree of diversity between beta 1 and beta 2 chains are suggested. The differences may be a consequence of selection pressures; this implies functional differences for products of the beta 1 and beta 2 loci. Alternatively, closely linked segments of the human class II region may differ in their underlying rates of variation, independent of selection pressures, and this may in part account for the extraordinary diversity found in the beta 1 first domain.

Alleles↗
PubMed1996

[Allelic and haplotypic polymorphism of HLA-DR].

In this short review, genomic organization of HLA-DR region is presented. Five main DR haplotypes are depicted in schematic figures listing alleles of active DRB genes in each haplotype group. Numbers of different DR molecules which can be produced in individuals possessing various haplotype combinations are shown.

Alleles↗
PubMed2002

Role of G protein beta3 subunit C825T and HLA class II polymorphisms in the immune response after HBV vaccination.

The G protein beta3 (GNB3) subunit and HLA are candidate genes predictive of immune response capacity. We therefore studied the influence of both gene systems on cellular and humoral immunity against hepatitis B virus (HBV) in 79 HBV booster-vaccinated healthy volunteers and an independent group of 77 probands after HBV basic immunization. Following booster vaccination, lymphocyte in vitro proliferation after stimulation with HBV surface antigen was 2.5-fold increased in GNB3 825T (TC + TT) vs CC allele carriers (P = 0.01) and was not influenced by HLA-DRB1 or DQB1 alleles. In addition, anti-HBs antibody titers in both groups were 2-fold increased in TC vs CC and decreased in TT vs CC allele carriers. However, antibody titers after HBV booster immunization were elevated in HLA-DQB1*0301 carriers (P corrected = 0.027). In summary, the GNB3 825T allele appears as a marker particularly predictive of cellular and HLA-DQB1*0301 of humoral immune responses following HBV vaccination.

Adult↗
PubMed1988

HLA-DP typing by analysis of DNA restriction fragment length polymorphisms in the HLA-DP beta subregion.

HLA class II antigens are encoded in the HLA-D region and are highly polymorphic. Southern hybridization technique was used to analyze restriction fragment length polymorphisms (RFLPs) in the DP beta gene and an attempt was made to correlate these with DP haplotypes derived from primed lymphocyte typing (PLT) analysis. Digestion of DNA from 32 Epstein-Barr virus (EBV)-transformed cell lines (of haplotypes DPw2, DPw3, DPw4, DPw5, and Cp63) with three different restriction endonucleases. Southern transfer, and hybridization to the DP beta cDNA probe revealed multiple fragments in all cell lines tested. The polymorphic patterns of these fragments were found to correlate with DP haplotypes, suggesting the possibility that the analysis of DNA RFLPs (DNA typing) in the HLA-DP beta subregion can distinguish and identify HLA-DP haplotypes.

DNA↗
PubMed1998

[HLA-DRB alleles polymorphism in susceptibility to asthma in Beijing Chinese].

OBJECTIVES: To investigate whether susceptibility or resistance to asthma associated with HLA-DRB alleles and analyze the relationship between HLA-DRB genes and clinical phenotype of asthma (TIgE, sIgE, BHR). METHODS: Using PCR-SSP(sequence-specific primer polymerase chain reaction), we tested the frequency distribution of HLA-DRB alleles in 50 asthmatic patients and 80 healthy volunteers from Beijing China. All patients had their serum TIgE, IgE antibody specific to house dust mite measured by RAST, bronchial responsiveness assessed by methacholine bronch-provocation (if FEV1% > or = 70%), and broncho-dilation measurement by inhaling salbutamol. RESULTS: There was significantly increased gene frequency of alleles DR6(13), DR52 in asthmatics compared with normal controls (17% vs 4.3%, P < 0.01; 50% vs 17.5%, P < 0.01), and RR was 7.55 and 4.7 respectively. The frequency of DR2(15), DR51 was lower in asthmatics than in controls (7% vs 18% P < 0.01; 2% vs 33.8% P < 0.01). The percentage of HLA haplotype DR6(13)-DR52 was higher in asthmatics than in healthy volunteers (20% vs 4%, P < 0.01, RR 6.4). 70% of individuals sharing DR6(13) gene and 56% of subjects carrying DR52 gene had elevated serum d1 sIgE antibody (> or = +4). There was no relationship between HLA-DRB alleles and total IgE, BHR. CONCLUSIONS: Alleles DR6(13), DR52 are significantly implicated in their susceptibility to asthma, at least they may be closely associated with this disorder. Conversely DR2(15), DR51 alleles might confer protection against asthma. Positive associations between DR6(13), DR52 and IgE response to d1 allergen are noted. HLA-DRB genes are particularly involved in regulating human atopic immune response.

Adult↗
PubMed2004

HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms.

The expression and importance of the non-classical human leukocyte antigen (HLA) class Ib gene, HLA-G, at the feto-maternal interface have been recognized. The HLA-G molecule is almost monomorphic and expressed in both membrane-bound and soluble isoforms. It has been shown to inhibit NK-mediated cell lysis and influence cytokine expression. Recently, a possible boarder immunoregulatory function of HLA-G also in adult life has been recognized. HLA-G gene polymorphism has been linked to differences in gene expression profile of alternatively spliced HLA-G transcripts and levels of specific HLA-G mRNA isoforms. On this background it is of general interest to further elucidate any associations between HLA-G polymorphism and protein expression. We have HLA-G genotyped 85 individuals attending IVF treatment, and further studied sHLA-G1/HLA-G5 and interleukin-10 (IL-10) in serum samples. In 21% of the serum samples sHLA-G1/HLA-G5 could be detected. There was no correlation between sHLA-G1/HLA-G5 and IL-10 concentrations in serum. Soluble HLA-G1/HLA-G5 was not detected in any samples homozygous for a 14-bp insertion polymorphism in exon 8 of the 3'-untranslated region (3'UTR) of the HLA-G gene ( P=0.03; Fisher's exact test). Polymorphisms in the 5'-upstream regulatory region (5'URR) of the HLA-G gene were also studied. In conclusion, this study indicates that polymorphisms in the 3'UTR and the 5'URR of the HLA-G gene may influence the expression of sHLA-G of possible importance in pathological pregnancies and also in organ transplantation.

3' Untranslated Regions↗
PubMed2004

HLA-DR B1 and DQ B1 polymorphisms in patients with coronary artery ectasia.

OBJECTIVES: The purpose of our study was to evaluate the significance of polymorphisms in HLA class II genes in coronary artery ectasia (CAE) patients. METHODS AND RESULTS: Twenty-six patients with CAE without associated cardiac defects were enrolled in the study. CAE was defined as luminal dilation of 1.5- to 2.0-fold of normal limits. Ninety-five healthy subjects who were donors for different organ transplantations, were chosen as control group. Physical examination, electrocardiography and chest X-ray were completely normal in these cases. Both the patients and the control group were screened and compared for their HLA class II genotypes. HLA-DR B1*13, DR16, DQ2 and DQ5 genotypes were significantly more frequent in the patient group. When the known risk factors of coronary heart disease were compared in the patients carrying these genotypes with the non-carrying group, no significant differences were encountered. CONCLUSIONS: HLA-DR B1*13, DR16, DQ2 and DQ5 may be associated with the pathogenesis and increase the risk of CAE.

Aged↗