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P Rahman

Publications and source records attributed to P Rahman.

At least 19 recordsLinked to original sources
PubMed2005

TNFalpha polymorphisms and risk of psoriatic arthritis.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a cytokine of critical importance in psoriatic arthritis. OBJECTIVES: (1) To examine the association between TNFalpha promoter gene polymorphisms and psoriatic arthritis in two well characterised Canadian populations with the disease; (2) to carry out a meta-analysis of all TNFalpha association studies in white psoriatic arthritis populations. METHODS: DNA samples were genotyped for five TNF variants by time of flight mass spectrometry using the Sequenom platform. All five single nucleotide polymorphisms were in the 5' flanking region of TNFalpha gene at the following positions: -1031 (T-->C), -863 (C-->A), -857 (C-->T), -308 (G-->A), and -238 (G-->A). Primary analyses were based on logistic regression. Summary estimates of disease/genotype relations from several studies were derived from random effects meta-analyses. RESULTS: 237 psoriatic arthritis subjects and 103 controls from Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto were studied. A combined analysis of data from both populations, showed a significant association between disease status and the -238(A) variant (p=0.01). The meta-analysis estimate for the -238(A) TNFalpha variant in eight psoriatic arthritis populations was also significant (odds ratio=2.29 (95% confidence interval, 1.48 to 3.55)). CONCLUSIONS: Analysis of TNFalpha variants in psoriatic arthritis populations shows that the -238 (A) variant is a significant risk factor for this disease.

Arthritis, Psoriatic↗
PubMed2005

Association of SEEK1 and psoriatic arthritis in two distinct Canadian populations.

OBJECTIVE: To examine the relationship between SNP +39604 in SEEK1 and psoriatic arthritis (PsA) in two distinct Canadian populations. METHODS: 103 patients with PsA and 105 ethnically matched controls from Newfoundland and 202 patients with PsA and 100 controls from Ontario were studied. Patients and controls were genotyped for SNP +39604 of SEEK1 by time of flight mass spectrometry, using the Sequenom platform. Genomic DNA was amplified by the Dynal RELI SSO HLA-Cw* typing kit for HLA-C typing. RESULTS: The frequency of the minor SEEK1(T) allele in subjects with PsA and controls was 48.5% and 32.4%, respectively (odds ratio (OR) = 2.0; p = 0.017), in the Newfoundland population and 46.5% and 38.0%, respectively (OR = 1.4; p = 0.16), in the Ontario population. Although SEEK1 is associated with PsA, particularly in the Newfoundland population, multivariate analysis showed that SEEK1 does not seem to be a further susceptibility factor if the HLA-Cw*0602 status is already known. No association was noted between SEEK1(T) allele and onset of psoriasis, PsA, or arthritis pattern. CONCLUSION: SEEK1 is associated with PsA in the Newfoundland founder population. This association is probably due to linkage disequilibrium between SEEK1 and HLA-Cw*0602 in this population.

Adult↗
PubMed2005

Genetic epidemiology of psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis (PsA) are interrelated disorders, as most patients with PsA also have psoriasis. Thus it is not surprising that epidemiological and immunogenetic studies have uncovered important links between these two disorders. Both disorders are highly heritable, and the prevalence of psoriasis is 19 times higher among first degree relatives of probands with PsA compared with the general population. Multiple human leucocyte antigen (HLA) associations are shared between psoriasis and PsA, though the magnitudes of these associations differ between the diseases. Genome-wide linkage studies have noted overlapping regions of significance for these two disorders within and outside the major histocompatibility complex (MHC) region. Thus, exploration of the genetic basis of psoriasis will likely strengthen the contention of an underlying genetic susceptibility for PsA and vice versa.

Arthritis, Psoriatic↗
PubMed2004

Bardet-Biedl syndrome 1 genotype and obesity in the Newfoundland population.

BACKGROUND AND OBJECTIVES: Obesity is one of the primary clinical features of Bardet-Biedl Syndrome (BBS), a genetically heterogeneous disorder that is usually inherited as an autosomal recessive trait. It has been suggested that heterozygous carriers of BBS are predisposed to obesity. We set out to identify the common mutation in BBS1 families from southwest Newfoundland and to examine the relationship between this mutation and obesity in the general population. METHODS AND SUBJECTS: We genotyped BBS1 families from Newfoundland to determine the nature of the mutation causing BBS in this population. We then screened 200 obese individuals (average body mass index (BMI)=37.9 kg/m2; average waist to hip ratio=0.935; average waist=113.8 cm) and 200 ethnically matched, unrelated, controls (average BMI=25.0 kg/m2; average waist to hip ratio=0.896; average waist=86.9 cm) from the same geographic region for the presence of this mutation. RESULTS: All affected members of the six Newfoundland BBS1 families were homozygous for the most common BBS1 mutation (M390R). This mutation was found in the heterozygous state in three of the 200 obese individuals and also in three of the 200 matched controls. CONCLUSIONS: The high frequency of BBS1 in Newfoundland appears to be the result of a founder event. Our data do not support the hypothesis that the M390R BBS1 mutation plays a significant role in the frequency of obesity in the general public in Newfoundland.

Adult↗
PubMed2003

Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis.

OBJECTIVE: Using humoral immune responses, Klebsiella pneumoniae has been implicated as a candidate microbial trigger in ankylosing spondylitis (AS) by several investigators but refuted by others. The objective of this case-control study was to compare the cellular (T-cell proliferation) and humoral (IgG and IgA, by ELISA) immune responses of affected individuals in multiplex AS families with those of unaffected family members and normal healthy controls in order to find out whether affected individuals exhibit a predominant immune response to K. pneumoniae. METHODS: Twenty-five families with two or more individuals affected with AS and 34 normal healthy controls matched with the affected family members for age, sex and ethnicity were enrolled in the study. All affected (n = 57) and unaffected (n = 37) family members had a detailed clinical evaluation. Peripheral blood was drawn to determine T-lymphocyte proliferation and the IgG and IgA (by ELISA analysis) immune responses to K. pneumoniae, Salmonella typhimurium, Yersinia enterocolitica and Chlamydia trachomatis. Immune responses to each of the four candidate organisms were compared in affected and unaffected individuals. Each individual was classified by the predominant antigenic immune response that they showed when comparison was made among the same concentrations of the four candidate microbial antigens. This stratification was then used (i) to compare immune responses in affected and unaffected family members and (ii) to compare clinical characteristics of affected family members. RESULTS: There was no difference in mean stimulation indices or antibody responses between affected and unaffected family members for each of the candidate organisms. In terms of predominant cellular immune responses to these organisms, there was no difference between affected and unaffected family members with respect to K. pneumoniae, C. trachomatis or Y. enterocolitica. However, a higher percentage of affected family members (25.9%) exhibited a predominant response to S. typhimurium compared with unaffected family members (5.9%, P < 0.02). In assessing antibody titres, K. pneumoniae was the predominant amongst these four organisms, but there was no difference between affected family members, unaffected family members and normal healthy controls. There was no relationship between immune responses and clinical characteristics. CONCLUSION: Our analysis of affected and unaffected family members in familial AS demonstrated no significant differences with respect to cellular or humoral immune responses to K. pneumoniae and three control microbes. In addition, K. pneumoniae did not exhibit a predominant immune response in affected individuals. Thus we find no supportive evidence to implicate a causal role for K. pneumoniae in familial AS.

Adult↗
PubMed2003

CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis.

A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA.

Adult↗
PubMed2001

HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

Adult↗
PubMed2001

Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus.

The aim of this study was to determine whether early damage accrued in SLE as measured by the SLICC/ACR Damage Index predicts mortality in an inception cohort of lupus patients that have been followed prospectively in a single centre. SLE patients from the University of Toronto Lupus Clinic presenting within 1 y of their diagnosis prior to 1988 were included. This enabled all patients to be potentially followed for at least 10 y. Yearly SLICC/ACR Damage Index scores were determined for each patient. Early damage was defined as a score > or = 1 and no damage as a score of 0 at the initial assessment. Log rank test was used to compare the survival experience between those with and without damage, with all patients being censored at 10 y. Two-hundred and sixty-three patients were identified in this inception cohort who were followed for 10 y. One-hundred and ninety patients (72%) had a SLICC/ACR Damage Index score of 0 (no damage) while 73 patients (28%) had at least one SLICC/ACR Damage Index item scored (early damage). Twenty-five percent of lupus patients who exhibited damage at their first SLICC/ACR Damage Index assessment died within 10 y of their illness as compared to only 7.3% who had no early damage (log rank P-value = 0.0002). SLE patients who died within 10 y were more likely to have renal damage (P = 0.013), and a trend toward more cardiovascular disease (P = 0.056), compared to patients who were alive. Early damage as reflected by the initial SLICC/ACR Damage Index is associated with a higher rate of mortality.

Adolescent↗
PubMed2001

Significance of isolated hematuria and isolated pyuria in systemic lupus erythematosus.

Hematuria or sterile pyuria as isolated urinary findings present a clinical dilemma for the treating physician. Our objective was to determine whether isolated hematuria and isolated sterile pyuria are associated with active systemic lupus erythematosus (SLE) with respect to renal and non-renal disease activity. This is a descriptive study from a large SLE cohort followed prospectively at the University of Toronto Lupus Clinic. All episodes of isolated hematuria and isolated pyuria between 1970 and 2000 were identified from our database. Isolated hematuria was defined as > 5 red blood cells per high power field; isolated sterile pyuria was defined as > 5 white blood cells per high power field in the absence of urinary infection and other renal manifestations. Non-renal disease activity (defined as nrSLEDAI > 1) was determined at first episode of isolated hematuria and pyuria. Renal disease activity was assessed by scoring renal biopsies within 3 months of detecting isolated hematuria or sterile pyuria. Thirty-four percent (323/946) of our cohort had at least one episode of isolated hematuria. Seventy-seven percent of these patients had concurrent non-renal disease activity. Of the 22 biopsies scored with isolated hematuria, 96% were abnormal (WHO > class I), including 52% with active nephritis. Twenty-three percent (215/946) had at least one episode of isolated sterile pyuria. Seventy-eight percent of these patients had concurrent non-renal disease activity. All 12 biopsies scored with isolated pyuria were abnormal (WHO Class > 1), including 75% with active nephritis. The appearance of isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. An ongoing debate has emerged regarding the significance of isolated hematuria and isolated pyuria with respect to SLE disease activity. The results of this study suggest that isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. Thus isolated hematuria and isolated sterile pyuria should be considered manifestations of active SLE.

Biopsy↗
PubMed2001

Comparison of radiological severity in psoriatic arthritis and rheumatoid arthritis.

OBJECTIVE: To compare the radiological severity of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Patients were identified from the University of Toronto PsA and RA databases. Using the earliest available radiographs, each RA patient was matched to a single PsA patient on the basis of sex, age, and disease duration. Two rheumatologists blinded to the patient's diagnosis scored the radiographs using the modified Steinbrocker method. RESULTS: PsA and RA groups were similar with respect to demographics as well as the use of disease modifying antirheumatic medications. No significant difference in Steinbrocker score for the hands and feet or the hands only was noted. Patients with RA had a higher radiological score in the feet. The 2 groups were similar in the number of joints with significant radiological damage (Steinbrocker 3 and 4). CONCLUSION; Overall the radiological severity in the hands and feet of patients with PsA was comparable to that of patients with RA.

Adult↗
PubMed2000

Probing for genes in seronegative spondyloarthropathy.

Seronegative spondyloarthropathies are a group of disorders characterized by inflammation of the spine, sacroiliac joints, and peripheral arthritis along with various characteristic extra-articular features. Their pathogenesis and immunogenetics have not yet been fully elucidated. Ankylosing Spondylitis (AS) is probably the best studied of these disease. It has now been 27 years since the association of human leukocyte antigen (HLA) B27 and AS has been demonstrated. Since then, a plethora of association studies and linkage studies unequivocally demonstrate that genetic determinants within or near the major histocompatible complex (MHC) are critical to the etiology of AS. Surprisingly though, the total MHC contribution to AS has been estimated at only 30%. In this review, we highlight the genetic basis of AS as the prototypical chronic axial arthritis, and discuss the rationale and approach in searching for non-HLA linked genes.

Diseases in Twins↗
PubMed2000

Vascular events in hypertensive patients with systemic lupus erythematosus.

Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE. SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy-related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event. One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (p = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4-24.8, P < 0.001). We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia.

Adolescent↗