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G Semana

Publications and source records attributed to G Semana.

68 records · Page 4Linked to original sources
PubMed1993

HLA-DR and -DQ genotyping by PCR-SSO in Shanghai Chinese.

The polymorphism of HLA class II (HLA-DRB1, -DQA1 and -DQB1) were investigated in 89 Shanghai Han Chinese using polymerase-chain reaction amplification and oligonucleotide (PCR-SSO) typing. Of the 43 DRB1 alleles tested, 24 were observed. DRB1*0901 (16.85%), *0803 (9.55%), *1202 (9.55%) and *1501 (12.92%) were most frequent and account for the high frequencies of DR9, DR8, DR5 and DR2 specificities in this population. The alleles DRB1*0101, *0102 and *1001 had very low frequencies. Among the 8 DQA1 and 13 DQB1 alleles tested, only DQA1*0401 and DQB1*0402 were absent. DQA1*0301, and DQB1*0301 and *0303 were among the most common alleles of the two loci respectively. Unusual DRB1-DQA1-DQB1 haplotypes were observed and a DRB1 "new" allele was suggested.

Alleles↗
PubMed1992

DPB1 polymorphism in rheumatoid arthritis: evidence of an association with allele DPB1 0401.

HLA-DP polymorphism was examined in 71 rheumatoid arthritis patients and 148 controls, using dot-blot analysis with 14 synthetic oligonucleotide probes specific for the variable region of the DPB1 second exon. The DPB1 0401 allele was found to be significantly more frequent in RA patients than in controls (77.46% vs 55.40%, p less than 0.002, pc less than 0.03, relative risk value: 2.74). An association between DPB1 0401 and seropositivity for rhumatoid factors was also observed: 44 of the 55 seropositive RA patients were DPB1 0401 (p less than 0.001). Analyzing the HLA DPB1 alleles frequencies in 57 HLA-DR-typed RA patients did not show any linkage between the DPB1 0401 and the DR4 specificities. Furthermore, the DPB1 0401 homozygous frequency was increased in DR4-negative RA patients. Our findings suggest an independent role of the DPB1 0401 allele in the genetic susceptibility to RA.

Adult↗
PubMed1992

No major monoclonal lymphocyte population in the thyroid of patients with Graves' disease: study of gene rearrangement by restriction fragment length polymorphism and polymerase chain reaction.

The present study aimed at determining the mono-, oligo-, or polyclonal nature of intrathyroid lymphocytes at the DNA level in patients with Graves' disease. Two techniques were used to seek monoclonal rearrangement in DNA derived from intrathyroidal lymphocytes obtained from six patients. The first was restriction fragment length polymorphism using two specific probes from the B-chain of T-cell receptor and the other from the heavy chain immunoglobulin gene; the second was polymerase chain reaction using a couple of specific primers from the variable and joining regions of heavy chain immunoglobulins. The results for the patients with Graves' disease were compared with those obtained for circulating T-and B-lymphocytes, granulocytes (negative controls), and T- and B-leukemic cells (positive controls). The results with restriction fragment length polymorphism favored a polyclonal origin for the lymphocytes in all cases, since no rearrangement was visualized. The results with polymerase chain reaction were analogous, and the technique was 10 times more sensitive in the detection of rearrangement.

Adult↗
PubMed1992

[Genetic susceptibility of insulin-dependent diabetes].

Type I Insulin-Dependent Diabetes Mellitus (IDDM) is an autoimmune disease characterised by the destruction of pancreatic Beta cells. There is an evidence for a contribution of genetic factors to the development of the disease and it is widely documented that HLA antigens contribute to the disease susceptibility. HLA-DR3 and HLA-DR4 associations have been firstly described in Caucasian. Recent studies at the gene level have elucidated this HLA association more precisely, pointing out the prominent role of HLA-DQ locus genes. The hypothesis has been proposed that some critical amino-acid at position 57 of DQ Beta chain and at position 52 of DQ Alpha chain both contribute to disease susceptibility. According to the functional role of HLA class II molecules, these particular residues may affect the antigen binding and T cell recognition and therefore contribute to the triggering of the pathological auto-immune response.

Autoimmunity↗
PubMed1991

Acute insulin response to intravenous glucose, glucagon and arginine in some subjects at risk for type 1 (insulin-dependent) diabetes mellitus.

The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a "normal" (n = 11; Group IIa) or a "low" insulin response to i.v. glucose (n = 10; Group IIb). Groups I and IIa displayed similar insulin responses to the three secretagogues. In contrast, Group IIb demonstrated lower insulin responses to both glucagon and arginine than control subjects (p less than 0.007 and p less than 0.04 respectively) or than "normo-responders" to glucose (p less than 0.007 and p less than 0.04 respectively). In Group IIb however, arginine-stimulated insulin release was increased compared to the response to glucose (p less than 0.006), while glucagon and glucose led to non-statistically different responses. Five "low-responders" developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p less than 0.05 and p less than 0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the "low-responders" who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p less than 0.006) or did not (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Aspartic acid at position 57 of the HLA-DQ beta chain in insulin-dependent diabetes mellitus: an association with one DRw9-DQw9 subtype in the Chinese population.

Eighteen unrelated Chinese patients with insulin-dependent diabetes mellitus (IDDM) were analyzed for HLA Class II genes using a variety of molecular biological techniques including restriction fragment length polymorphism (RFLP), polymerase chain reaction with allele-specific oligonucleotides (PCR-ASO) and direct DNA sequencing. The high frequency of DR3/DR4 heterozygotes found in the Chinese with IDDM strengthens the importance of this combination of haplotypes in IDDM susceptibility since it is present in two genetically distant populations--Chinese and Caucasians. The frequency of DRw9, a rare allele in the Caucasian population, is much higher in the Chinese. Moreover, the DQ beta chain linkage of DRw9 was different in IDDM patients compared with control subjects. In contrast with previous results, codon 57 of the DQ beta chain was aspartic acid in DRw9 Chinese IDDM patients. Furthermore, one particular DRw9-DQw9 haplotype may be associated with IDDM susceptibility in the Chinese population.

Alleles↗
PubMed1991

[A focus of multiple sclerosis in Bretagne: HLA markers and evaluation of consanguinity].

In a previous study, we established the overall prevalence of multiple sclerosis at 25 per 100,000 inhabitants in the French province of Brittany and found that the geographical distribution was uneven with four circumscribed high prevalence areas with more than 45 per 100,000. We conducted the present study to try to ascertain whether the existence of such clusters of MS could be explained by genetic factors, using two ways: the major histocompatibility markers and the frequency of intermarriage. Among the four areas of high prevalence, we examined the one with the highest prevalence, exempt from migratory movements over the last 100 years. We compared this studied population to a sample of 1005 healthy unrelated individuals coming from all over Brittany, designated as general Brittany population. A large sampling (about 25%) of the population accepted to take part in the study. Regarding HLA markers, we observed in the high prevalence area an increases percentage of B7, B8, B12, DR4 and a decreased percentage of B5, compared with the Brittany control population. The consanguinity coefficient in the population of high MS prevalence area was steadily much higher than the one in neighbouring areas with a low MS prevalence during a long period from 1896 to 1945. Under the reserve of non-randomized sampling of individuals for HLA marker study, our findings yielded a double argument in favor of genetic factors influencing the presence of clusters of MS cases: the particularities of HLA phenotype pattern and the increased consanguinity coefficient. The particularities of HLA polymorphism observed in the high prevalence area are likely to be the consequence of the intermarriage habits of this population.

Adult↗
PubMed1990

Implication of the HLA-DRB3 gene in Graves' disease: predominance of allele Dw24.

Using RFLP, the present study sets off to determine the MHC class II gene polymorphism in Graves' disease, in order to define the HLA-related genetic susceptibility. Considering the preferential link between Graves' disease and the HLA-DR3 antigen, 42 HLA-DR3 Graves' disease patients were studied and compared with 42 HLA-DR-matched controls. Hybridization with a DQ alpha probe of DNAs digested by Taq I revealed a polymorphism of the DR3 haplotype with an overrepresentation of a 2.1 kb(U) fragment in patients, but this was merely a sign of the linkage disequilibrium between U and B8DR3. Hybridization with the DR beta probe of DNAs digested by Taq I yielded more facts. It revealed the overrepresentation of the Dw24 specificity (Taq I:9.8 kb) in DR3 Graves' disease patients. This study thus enabled us to determine precisely the susceptibility linked to the DR3 haplotype, implicating the DRB3 gene and its Dw24 allele, which appear to be the most reliable markers of the disease, providing a higher relative risk than B8DR3.

Alleles↗
PubMed1988

Definition of DRw10 specificity by restriction fragment length polymorphism.

The purpose of this study was the RFLP characterization of the DRw10 specificity. Twenty-two DRw10 cells were tested: the DNAs were digested by seven restriction enzymes and hybridized with DR beta, DQ beta and DQ alpha probes. Hybridization with DR beta revealed a pattern particular to the DRw10 specificity, with a specific TaqI 12.5Kb fragment. Hybridization with both DQ-specific probes showed that DRw10 is always associated with a special DQw1 subtype: DQw5. Furthermore, at DR and DQ levels, the 22 DRw10 cells behaved homogeneously.

Alleles↗
PubMedDate not supplied

Predictive value of age-related acute insulin response to glucose in subjects at risk for type 1 diabetes: results of a 6-year follow-up study from west-France.

The acute insulin response to i.v. glucose (AIRG) was evaluated in 344 first-degree relatives of patients with Type 1 diabetes. In 318 relatives aged 3 to 48 years without islet cell antibody and insulin autoantibody, correlations (p < 0.0006) were found between age and fasting insulinaemia, fasting glycaemia, or AIRG, with a peak during puberty. Assuming that these relatives without islet cells and insulin auto-antibodies have a low risk of developing Type 1 diabetes, we provided a "standard age-related chart" for AIRG with a "low" AIRG defined as a value below the 1st percentile for each pubertal stage. Using these cut-off points, predictive characteristics of a low AIRG for progression towards diabetes within 6 years were analysed. Four relatives developed diabetes and one displayed impaired oral glucose tolerance. Four out of these 5 subjects had islet cell and insulin auto-antibodies, but the other one was negative for these markers. Three of these 5 subjects had low AIRG at entry (30, 24 and 1 months before diabetes, respectively). The two others displayed a steady progressive decline (p < 0.02) of age-related during the follow-up before impaired oral glucose tolerance and diabetes appeared (rate of decline: 15 microU/ml/year). Thus, independently of the presence of islet cell antibodies, the predictive value of a low age-related AIRG during the follow-up is greater than the single low AIRG at entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

DRB1*15 and DRB1*03 extended haplotype interaction in primary Sjögren's syndrome genetic susceptibility.

OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease with a genetic component. Among the genetic factors, the role of HLA class II genes has been suggested and a positive association with DRB1*03 allele has been described. However, there is no consensus on a unique HLA locus for this disease nor on the role of the HLA gene product in the disease. The aim of this study was to analyse prospectively MHC region involvement in the genetic susceptibility to SS by studying DRB1, DQB1, DPB1, TAP1, TAP2 genes and TNF microsatellites in a population of 45 primary SS patients. METHODS: All the polymorphisms studied were analysed at the genomic level using PCR-based methodologies. RESULTS: Concerning HLA class II alleles, the highest relative risk to develop the disease was associated with the DRB1*15-DRB1*0301 heterozygous genotype (17.8% vs 3.5% in controls - pc < 0.005, OR = 5.96). Analysing other genes located on the same region allowed us to further determine the DRB1 haplotypes at risk. For instance, the DRB1*0301 haplotype involved in the genetic susceptibility to SS was more often associated with the DPB1* 0201 and TNF-a2 alleles in SS patients than in controls. Moreover, all the DRB1*15-DRB1*0301 SS patients were TAP1-0101, TAP2-0101 homozygous, allowing us to deduce the extended genotype at risk as DRB1*15, TAP1-0101, TAP2-0101/DRB1*0301, TAP1-0101, TAP2-0101 which was carried by only 3 controls out of the 130 tested (p < 0.01, OR = 6.68). CONCLUSION: This study confirmed the role of the MHC region in the susceptibility to Sjögren's disease, and for the first time suggests a synergistic interaction between two HLA-DRB1 extended haplotypes in the genetic mechanisms controlling the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗