PubMed Health⌕ Search

Biomedical subjects

Anne Barton

Publications and source records attributed to Anne Barton.

25 records · Page 2Linked to original sources
PubMed2004

Genetic epidemiology of psoriatic arthritis.

Psoriatic arthritis (PsA) is defined as an inflammatory arthritis (IA) associated with psoriasis and is usually negative for rheumatoid factor. This ambiguous definition has impeded research into this subject, but as yet no agreed definition or classification criteria exist for PsA. Furthermore, there are those who question whether PsA exists as a distinct disease, or is a mere coincidence of inflammatory arthritides such as rheumatoid arthritis or ankylosing spondylitis with psoriasis. The pathogenesis of both IA and psoriasis is complex, involving interactions between many different genes and environmental etiological factors. It is likely that PsA is also a complex disease. The identification of genetic susceptibility factors unique to PsA over and above those that contribute to IA or psoriasis alone would put an end to speculation as to whether PsA exists as a distinct disease. In addition, it may aid in the development of novel therapies which target PsA specifically. This review summarizes the approaches taken to identify PsA susceptibility genes, and outlines some interesting regions which may harbor PsA susceptibility genes.

Journal Article↗
PubMed2004

Polymorphisms in the mannose binding lectin (MBL) gene are not associated with radiographic erosions in rheumatoid or inflammatory polyarthritis.

OBJECTIVE: To investigate the association between the mannose binding lectin gene (MBL) promoter and structural single nucleotide polymorphisms (SNP) with development of erosions in a primary care inception cohort of patients with inflammatory polyarthritis (IP). METHODS: DNA was available from 438 patients with IP and radiographic data were available for all patients at 5 years. Four SNP [MBL-550*C/G (H/L), MBL-221*G/C (Y/X), MBL codon 52*C/T, and MBL codon 54*G/A] mapping to the MBL gene were genotyped using primer extension techniques. Allele frequencies were compared between IP cases with erosions by 5 years and those without. RESULTS: None of the SNP were associated with erosive outcomes by 5 years. Furthermore there was no association with Larsen score by 1 or 5 years or with the change in Larsen score between 1 and 5 years. Similarly, the genotype combinations known to encode for low MBL protein production were not associated with erosive outcome in the IP cohort as a whole or in those with rheumatoid arthritis (RA) by 5 years. CONCLUSION: Polymorphism within the MBL gene is not associated with presence or extent of erosions by 5 years in patients with RA or IP.

Adult↗
PubMed2003

Linkage analysis of cross-sectional and longitudinally derived phenotypic measures to identify loci influencing blood pressure.

BACKGROUND: The design of appropriate strategies to analyze and interpret linkage results for complex human diseases constitutes a challenge. Parameters such as power, definition of phenotype, and replicability have to be taken into account in order to reach meaningful conclusions. Incorporating data on repeated phenotypic measures may increase the power to detect linkage but requires sophisticated analysis methods. Using the simulated Genetic Analysis Workshop 13 data set, we have estimated a variety of systolic blood pressure (SBP) phenotypic measures and examined their performance with respect to consistency among replicates and to true and false positive linkage signals. RESULTS: The whole-genome scan conducted on a dichotomous hypertension phenotype indicated the involvement of few true loci with nominal significance and gave rise to a high rate of false positives. Analysis of a cross-sectional quantitative SBP measure performed better, although genome-wide significance was again not reached. Additional phenotypic measures were derived from the longitudinal data using random effects modelling for censored data with varying levels of covariate adjustment. These models provided evidence for significant linkage to most genes influencing SBP and produced few false positive results. Overall, replicability of results was poor for loci, representing weak effects. CONCLUSION: Longitudinally derived phenotypes performed better than cross-sectional measures in linkage analyses. Bearing in mind the sample design and size of these data, linkage results that fail to replicate should not be dismissed; instead, different lines of evidence derived from complementary analysis methods should be combined to prioritize follow up.

Adult Children↗
PubMed2003

Approaches to identifying genetic predictors of clinical outcome in rheumatoid arthritis.

Predicting which patients with rheumatoid arthritis (RA), at presentation, are likely to suffer a severe disease course based on genotype data would be a major clinical advance. It would ensure that patients at highest risk of a severe outcome could be targeted with early aggressive therapies. With a better understanding of interactions between genotype and drug response it would be possible to prescribe treatments most likely to be efficacious and safe for specific patient subgroups. While a clear genetic component has been demonstrated in RA severity, the identification of genetic factors poses a challenge to researchers in the field. Initiatives such as the SNP Consortium and advances in genotyping technology have facilitated the investigation of genetic factors in both disease susceptibility and severity. However, several other factors, such as the availability of suitable longitudinal cohorts, definition of outcome measures, study design, selection of genetic markers, and statistical power, will all contribute to the likely success of genetic studies. Several strategies that have been applied in the pursuit of genetic predictors of clinical outcome in RA. While some encouraging results have been generated, it has so far been difficult to quantify the predictive value of genetic markers and extrapolate the results from genetic studies to clinic patients. Establishing high quality prospective inception cohorts, a more systemic approach to defining suitable outcome measures, and understanding the effects of treatment, will be critical to the eventual identification of good predictive genetic markers.

Animals↗
PubMed2002

Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom.

OBJECTIVE: To undertake a systematic whole-genome screen to identify regions exhibiting genetic linkage to rheumatoid arthritis (RA). METHODS: Two hundred fifty-two RA-affected sibling pairs from 182 UK families were genotyped using 365 highly informative microsatellite markers. Microsatellite genotyping was performed using fluorescent polymerase chain reaction primers and semiautomated DNA sequencing technology. Linkage analysis was undertaken using MAPMAKER/SIBS for single-point and multipoint analysis. RESULTS: Significant linkage (maximum logarithm of odds score 4.7 [P = 0.000003] at marker D6S276, 1 cM from HLA-DRB1) was identified around the major histocompatibility complex (MHC) region on chromosome 6. Suggestive linkage (P < 7.4 x 10(-4)) was identified on chromosome 6q by single- and multipoint analysis. Ten other sites of nominal linkage (P < 0.05) were identified on chromosomes 3p, 4q, 7p, 2 regions of 10q, 2 regions of 14q, 16p, 21q, and Xq by single-point analysis and on 3 sites (1q, 14q, and 14q) by multipoint analysis. CONCLUSION: Linkage to the MHC region was confirmed. Eleven non-HLA regions demonstrated evidence of suggestive or nominal linkage, but none reached the genome-wide threshold for significant linkage (P = 2.2 x 10(-5)). Results of previous genome screens have suggested that 6 of these regions may be involved in RA susceptibility.

Arthritis, Rheumatoid↗
PubMed2002

Genetic approaches to the investigation of rheumatoid arthritis.

The investigation of genetic factors affecting the development or severity of rheumatoid arthritis may give new insights into the pathways involved in disease pathogenesis and lead to the identification of novel therapeutic targets. Recently, several novel approaches have been used in the attempt to unravel the complex association of rheumatoid arthritis with the human leukocyte antigen ( HLA ) gene region. It is clear that non-HLA genes are also involved in disease pathogenesis, and identifying them remains a challenge. In the past year, considerable headway has been made in this field, and some interesting strategies have been used. This review summarizes the results of many of the HLA and non-HLA studies and tries to draw lessons from the investigation of genetic susceptibility factors in other complex diseases.

Arthritis, Rheumatoid↗