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W Thomson

Publications and source records attributed to W Thomson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms.

OBJECTIVE: To determine whether giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are associated with different tumor necrosis factor (TNF) microsatellite polymorphisms. METHODS: Typing of TNF microsatellite polymorphisms was carried out by molecular-based techniques on DNA obtained from a population sample of residents from Lugo, northwestern Spain. A case-control approach was used to compare 136 patients with GCA and/or PMR with 147 ethnically matched controls. The association of disease with TNF microsatellite polymorphisms was investigated using chi-square tests and multivariate logistic regression analyses. RESULTS: Different TNF microsatellite associations were found with GCA and PMR. In patients with isolated GCA, the primary association was with TNFa2, which was independent of the GCA associations with HLA-DRB1*0401 and *0101. A negative association was found with TNFa10. In patients with isolated PMR, there was a positive association with TNFb3. This was found to be independent of the HLA-DRB1*13/*14 association in isolated PMR. TNFd4 was negatively associated with isolated PMR. Forward stepwise logistic regression analyses indicated that the strongest association with GCA was provided by the TNFa2 allele, although DRB1*0401 and *0101 were still associated. PMR was primarily associated with TNFb3. A direct comparison of TNF allele frequencies between isolated GCA and isolated PMR indicated that the main difference between these conditions occurred in the frequency of TNFa10. CONCLUSION: GCA and PMR in individuals from northwestern Spain are associated with different TNF microsatellite polymorphisms. The primary TNF associations (TNFa2 and TNFb3) appear to influence susceptibility to these conditions independent of any HLA-DRB1 association.

Aged↗
PubMed2000

Effects of alendronate on bone density in men with primary and secondary osteoporosis.

Alendronate has been reported to increase bone mineral density (BMD) and reduce fracture risk in women with osteoporosis. As there are no proven safe and effective treatments available for men with osteoporosis, we compared the effects of alendronate (10 mg/day) on BMD, measured using dual-energy X-ray absorptiometry, in a 12-month prospective, controlled, open label study involving (i) men with primary (n = 23) or secondary osteoporosis (n = 18), (ii) postmenopausal women with primary (n = 18) or secondary (n = 21) osteoporosis, and (iii) 29 male and 14 female untreated controls matched by age, height and weight. The patients had one or more vertebral fractures and ranged in age from 34.6 to 85.1 years. BMD was detectably increased relative to baseline by 6 months, and increased by comparable amounts in males and females with primary or secondary osteoporosis. At 12 months, lumbar spine BMD was 5.4% +/- 1.1% to 7.0% +/- 2.2% higher in the treated groups compared with baseline and controls (p < 0.05 to 0.0001). Trochanteric BMD increased by 2.6% +/- 1.5% and 3.7% +/- 1.7% in treated men with primary and secondary osteoporosis, respectively (p = 0.06 to 0.08), and by 3.9% +/- 1.3% in treated women with primary osteoporosis (p < 0.01) after 12 months. No significant changes were detected at the femoral neck or Ward's triangle. BMD remained unchanged in controls. We infer that alendronate has comparable incremental effects on BMD in men and women with primary and secondary osteoporosis within 12 months of treatment. The changes are in the order of 0.5 SD--effects associated with a clinically worthwhile reduction in fracture risk. The data provide room for optimism regarding the role of alendronate in the treatment of osteoporosis in men. Randomized, double-masked and placebo-controlled trials are needed to confirm these preliminary findings and demonstrate antifracture efficacy using vertebral and nonvertebral fracture rates as the primary endpoint.

Absorptiometry, Photon↗
PubMed2000

DLA-DQA1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP).

Several recent studies have identified DNA sequences for alleles of the DLA-DQA1 locus in the dog. To date, 10 DQA1 alleles have been reported. No data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether alleles are breed specific. We have addressed this issue by establishing a molecular-based sequence-specific oligonucleotide probing (SSOP) method to identify all published DQA1 alleles and have used these methods to type a large number of dogs. Oligonucleotide probes were designed to detect all the polymorphic sites in exon 2. This allowed assignment at the allele level. Three hundred and thirty dogs were typed for DQA1. All but two of the published DQA1 alleles were identified in these animals. One new allele was identified, and confirmed by DNA cloning and sequencing. This typing method provides a powerful tool for generating data that will be essential for studies investigating the genetic relationships between different breeds.

Animals↗
PubMed2000

Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients.

The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. RA patients (n=179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n=145) were recruited. RA susceptibility in this population was predominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04. The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner. Logistic regression analyses revealed that the TNF microsatellite markers TNFc1 and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF c1 allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals. TNFc1 and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFc1) polymorphism seemingly associated with low TNFalpha production, is a risk factor for RA.

Adult↗
PubMed2000

Nomenclature for factors of the dog major histocompatibility system (DLA), 1998: first report of the ISAG DLA Nomenclature Committee.

A Nomenclature committee for Factors of the Dog Major Histocompatibility System or Dog Leukocyte Antigen (DLA) has been convened under the auspices of the International Society for Animal Genetics (ISAG) to define a sequence based nomenclature for the genes of the DLA system. The remit of this committee includes: assignment of gene names rules for naming alleles assignment of names to published alleles assignment of names to new alleles rules for acceptance of new alleles DLA Nomenclature Committee, rules for acceptance, DLA genes and alleles, sequence based nomenclature.

Alleles↗
PubMed2000

Identification of further DLA-DRB1 and DQA1 alleles in the dog.

Three novel DLA-DRB1 alleles and one novel DQA1 allele have been identified in a panel of 367 dogs. These were suggested by unusual reaction patterns found in sequence specific oligonucleotide probing (SSOP) data. Four new alleles were confirmed using DNA cloning and sequencing.

Alleles↗
PubMed2000

Mannose binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids.

Mannose binding lectin (MBL) gene and promoter-region polymorphisms contribute to a reduction in the levels of circulating MBL in a number of ways. Promoter polymorphisms affect the levels of MBL produced, whilst structurally encoding mutations cause non-functional protein to be assembled and subsequently degraded. MBL is important as a protein of the innate immune system in both the clearance of potential pathogens and the activation of the complement cascade. Using variations of SSP-PCR amplifications and SSO probing techniques, we have produced MBL-polymorphism haplotype and genotype profiles of a series of high-level MBL-producing, low-level MBL-producing and random individuals taken from a population of 800 UK Caucasoid controls. Structurally encoding mutant alleles were more frequent within the low-level producing cohort when compared to both high-level producers and the randomly selected sample. However, not all low-level producers could be accounted for by the possession of low-level encoding haplotypes. This may be due to the presence of additional, undetected polymorphisms governing MBL production, or another external factor that may influence the transcriptional regulation of the gene.

Alleles↗
PubMed2000

Association between HLA-DRB1*15 and secondary Sjögren's syndrome in patients with rheumatoid arthritis.

OBJECTIVE: To examine the relationship between HLA-DRB1 alleles and the clinical expression of the secondary form of Sjogren's syndrome (SS) in patients with rheumatoid arthritis (RA). METHODS: Typing of HLA-DRB1 alleles was carried out by molecular based techniques on DNA obtained from a population of patients with RA from Lugo in northwestern Spain. Patients were diagnosed according to the 1987 American College of Rheumatology criteria for RA, and comprised 137 seropositive and 42 seronegative individuals. Secondary SS was defined by xerostomia and keratoconjunctivitis sicca, supported by ophthalmologic examination. Patients were compared with 145 ethnically matched controls. RESULTS: Twenty-two (12.3%) of the patients with RA also had secondary SS. The majority of these (19/22) were rheumatoid factor positive. Eleven (57.9%) of the seropositive patients with secondary SS carried an HLA-DRB1*15 allele compared with 28 (23.7%) seropositive patients without secondary SS (OR 4.4, 95% CI 1.5-13.6, pc = 0.014). In contrast, the frequency of DRB1*04 was reduced in seropositive patients with secondary SS compared to those without secondary SS, although this did not achieve significance after correction for multiple testing (OR 0.28, 95% CI 0.09-0.88, pc = 0.08). Of note, in individuals lacking the RA shared epitope (SE), DRB1*15 was found to be associated (OR 2.3, 95% CI 1.0-5.1, pc = 0.03) with RA in the absence of secondary SS. No differences were found between DRB1*15 positive and negative patients in terms of erosive disease, nodules, or rheumatoid factor positivity. CONCLUSION: Secondary SS is associated with an increased frequency of HLA-DRB1*15 in seropositive patients with RA from northwestern Spain. HLA-DRB1*15 is also associated with RA in SE negative individuals without secondary SS, although the possibility that such patients will later develop SS cannot be ruled out. Further studies are needed to confirm whether the HLA-DRB1*15 association with secondary SS in RA is common to Spanish and other ethnic populations.

Aged↗
PubMed2000

Maternal-fetal HLA incompatibility and the course of inflammatory arthritis during pregnancy.

OBJECTIVE: Studies indicate that maternal-fetal incompatibility of HLA-DR and DQ antigens may be associated with a decreased risk of disease activity during pregnancy in women with rheumatoid arthritis. We attempted to replicate these findings in a large cohort of women with inflammatory polyarthritis. METHODS: Women with an inflammatory polyarthritis were recruited during the last trimester of pregnancy and were interviewed and examined in their homes by a research nurse. Each woman provided a sample of blood as well as permission for a sample of cord blood to be taken at the time of birth. DNA was extracted from both maternal and cord blood and HLA-DRB1 and DQB1 typing performed. On the basis of known haplotypes found in Caucasian populations, DQA1 type was inferred wherever possible. RESULTS: Based on 110 or more maternal-fetal pairs, there was no increased occurrence of disease remission associated with maternal-fetal incompatibility of DRB1 alleles (remission ratio 0.7, 95% confidence interval 0.2-2.8), DQB1 alleles (remission ratio 1.2, 0.3-6.5), or DQA1 alleles (remission ratio 0.8,0.3-1.9). Results were similar whether maternal-fetal sharing was defined by broad allelic group or by specific alleles. CONCLUSION: Our results do not support the hypothesis that maternal-fetal HLA incompatibility contributes to remission of inflammatory arthritis during pregnancy.

Adult↗
PubMed1999

Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog.

Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on individual allele frequencies exists, either for specific breeds or cross breeds, and the full extent of the polymorphism at each of these loci is still not known. We have used sequence-specific oligonucleotide probing (SSOP) to characterise a series of 367 dogs for their DRB1 and DQA1 alleles. These included individual animals from over 60 different breeds, with numbers per breed ranging from 1 to 39. DLA types were generated from 218 dogs for DRB1 and from 330 dogs for DQA1, while 181 dogs were characterised for both these loci. The frequency of individual DRB1 and DQA1 alleles showed considerable interbreed variation, e.g. 83% of West Highland White Terriers were DRB1*01 as opposed to 9% of Collies. No breed had >9 of the 22 DRB1 types defined in this study; several breeds had only two DRB1 types. DLA-DQA1 showed less variation in allele numbers per breed, but also showed considerable interbreed frequency variation. Haplotype analysis revealed over 44 different DRB1/DQA1 combinations. Of these, 25 were in a number of animals, and also in an animal that was homozygous for one or both of these loci. Some DRB1 alleles could be found in combination with several different DQA1 alleles, while others were only present in one haplotypic combination. DLA allele frequency data in normal dogs will be critical for disease association studies. It may also be possible to use haplotype data to establish the genetic relationships between different dog breeds.

Alleles↗
PubMed1999

Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthritis: results from a large, population-based study.

OBJECTIVE: To accurately determine the contributions of HLA-DRB1 alleles in explaining susceptibility to inflammatory polyarthritis in a large, true population-based cohort of new-onset cases. METHODS: A cohort of 680 consecutive patients with inflammatory polyarthritis, of whom 404 satisfied the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), was recruited from the population-based Norfolk Arthritis Register. All cases were compared with 286 local population controls. A standardized clinical assessment was performed on all patients. HLA-DRB1 phenotypes, including DR4 subtypes, were determined using a semiautomated, reverse dot-blot method. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was only a modest association (OR 1.8, 95% CI 1.4-2.4) between inflammatory polyarthritis and the presence of any shared epitope (SE) allele; the strongest individual risk was with DRB1*0404 (OR 3.5, 95% CI 1.8-6.8). Comparison of the genotypes demonstrated that the effect of being SE homozygous (OR 2.1, 95% CI 1.5-3.0) was only moderately greater than the effect of being SE heterozygous (OR 1.3, 95% CI 1.1-1.6). The exception to this was genotypic combinations that included HLA-DRB1*0404, which exhibited ORs ranging up to 18.0. There were no differences between either the phenotype or genotype data when the patients were stratified by RA status (defined by the ACR criteria). In contrast, the associations were substantially stronger in patients who were positive for rheumatoid factor. CONCLUSION: Previous studies had not been able to clarify whether the influence of HLA-DRB1 on RA was related to disease susceptibility or to disease severity and progression. These data on a unique population-based incident cohort suggest only weak effects on susceptibility, with the exception of the clearly distinct influence of HLA-DRB1*0404.

Alleles↗
PubMed1999

The influence of HLA-DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis.

OBJECTIVE: There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis. The exact role of these alleles in short-term outcome is determined in this large, prospective, population-based study. METHODS: We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods. Disease outcome was assessed at 2 years in terms of persistent joint inflammation, functional disability, and radiologic erosions. Results are expressed as risk ratios (RR) with 95% confidence intervals (95% CI). RESULTS: There was no influence of HLA-DRB1 alleles, in any combination, on the likelihood of disease persistence, and only a modest effect on functional disability (Health Assessment Questionnaire score > or = 1). The most obvious effect was on the development of erosions (RR 1.9, 95% CI 1.4-2.6 for those who carried at least 1 DRB1 shared epitope [SE] allele), with slightly greater effects for those who were homozygous for SE-bearing alleles (RR 2.5, 95% CI 1.8-3.6). This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor. Among patients with erosions, HLA-DRB1 had no influence on the severity of radiologic damage (defined as the number of eroded joints, or total Larsen score). CONCLUSION: These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease.

Adolescent↗
PubMed1999

DLA-DRB1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP).

To date, DNA sequences for 29 dog DLA-DRB1 alleles have been reported. However, no data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether there is interbreed variation of allele distribution. We have addressed this by establishing a molecular based sequence-specific oligonucleotide probing (SSOP) method to identify all of the known broad DRB1 types and we have used this to type a random panel of dogs. A series of oligonucleotide probes were designed to detect known polymorphisms in the three DRB1 hypervariable regions, together with two distinctive motifs in other regions of exon 2. This set of probes enabled us to assign broad DRB1 types. Two hundred and eighteen dogs were SSOP typed for DRB1. All but 4 of the published DLA-DRB1 alleles were identified in these animals. Interbreed variation in both allele distributions and allele frequencies were observed, which may be useful in the study of genetic variation between breeds. This variation also has implications for the selection of control groups for studies aimed at identifying MHC associations with disease susceptibility in the dog.

Animals↗
PubMed1999

Nomenclature for factors of the dog major histocompatibility system (DLA), 1998. First report of the ISAG DLA Nomenclature Committee. International Society for Animals Genetics.

A Nomenclature Committee for factors of the dog major histocompatibility system or dog leukocyte antigen (DLA) has been convened under the auspices of the International Society for Animal Genetics (ISAG) to define a sequence-based nomenclature for the genes of the DLA system. The remit of this committee includes: i) assignment of gene names; ii) rules for naming alleles; iii) assignment of names to published alleles; iv) assignment of names to new alleles; and v) rules for acceptance of new alleles.

Amino Acid Sequence↗
PubMed1999

The Bg/II polymorphism of the human prolactin gene lies within intron C and can be detected by PCR/RFLP.

Prolactin has been shown to be active as an immunomodulatory hormone and is therefore of potential importance in disease progression and development. Any polymorphism in the gene and regulatory sequences may prove useful for disease association studies. A Bg/II polymorphism has been previously detected within the prolactin gene region. We have mapped this polymorphism to intron C and detected the base mutation that causes it. We have also developed a PCR-RFLP method to genotype individuals.

Alleles↗
PubMed1999

The influence of HLA-DRB1 alleles encoding the DERAA amino acid motif on radiological outcome in rheumatoid arthritis.

OBJECTIVES: To investigate the influence of HLA-DRB1 alleles encoding the QK/RRAA shared epitope (SE) on radiological outcome in rheumatoid arthritis (RA), and to determine whether it is modulated by alleles carrying the putative rheumatoid arthritis-protective (RAP) sequence DERAA. Patients and methods. The association between erosive damage and HLA-DRB1 status was examined in 315 RA patients with a disease duration of 5-30 yr. Radiological outcome was measured by scoring X-rays of the hands and feet using the standard radiographs of Larsen (Larsen score). HLA-DRB1 typing was carried out using polymerase chain reaction methodology. RESULTS: Patients with two alleles encoding the QK/RRAA SE had significantly higher Larsen scores than SE-negative patients (96.9 vs 83.3; P=0.04, after correction for multiple testing), with DRB1*0401/*0401 homozygotes demonstrating the greatest radiological damage (99.9). The lowest Larsen score (65.6) was observed in patients carrying the DERAA motif without an accompanying SE allele (RAP+/SE-). This was significantly lower than in patients with RAP+/SE+ (105.6; P=0.04), RAP-/SE- (88.2; P=0.05) and RAP-/SE+ (95.8; P=0.009), after correction for multiple testing. There was no evidence that the RAP sequence was modulating the effect of the SE since radiological outcome in RAP+/SE+ patients was not significantly different to that in RAP-/SE+ individuals. CONCLUSIONS: Our data support a possible role for DRB1 alleles encoding the DERAA motif in protection against severe erosive damage in patients lacking the QK/RRAA SE, but not in patients heterozygous for the SE. This suggests that DRB1 alleles encoding the SE have a dominant influence over 'protective alleles' and are not merely 'non-protective'.

Alleles↗
PubMed1999

Absence of association between interleukin 1 alpha and oligoarticular juvenile chronic arthritis in UK patients.

OBJECTIVE: To determine whether interleukin 1 alpha (IL-1alpha) polymorphisms are associated with UK oligoarticular juvenile chronic arthritis (JCA). PATIENTS AND CONTROLS: A well-characterized population of 164 UK Caucasian oligo-JCA patients and a control panel of 173 unrelated healthy UK Caucasian individuals. METHODS: The IL-1alpha promoter mutation at -889 was examined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The cases and controls were also genotyped for an IL-1alpha intronic microsatellite repeat. RESULTS: No association was observed between IL-1alpha polymorphisms and UK oligoarticular JCA patients. In particular, no association between IL-1alpha polymorphisms and chronic anterior uveitis was found. CONCLUSIONS: IL-1alpha is not associated with oligoarticular JCA in UK patients. This differs markedly to findings for IL-1alpha in Norwegian JCA patients.

Adult↗