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Biomedical subjects

Ali H Hajeer

Publications and source records attributed to Ali H Hajeer.

At least 19 recordsLinked to original sources
PubMed2006

The significance of documenting clinical appearance of the uterine cervix in the cervical cytology form.

OBJECTIVE: To determine whether or not the Pap smear taker is reporting the clinical appearance of the cervix on the cytology request form, and if cytologist / smear taker are giving any importance to this information prior to issuing advice on subsequent follow-up. Finally, to evaluate the clinicians' response to normal Pap smear report in the absence of the clinical comment on the cervix. METHODS: A retrospective study, for a total of 1196 random smear results performed between 1999 and 2000 at King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with its relevant charts were evaluated. The samples were divided into 2 main groups. Group I, the Pap smears sent with the absence of clinical description of the cervix, and group II, was sent with the clinical description of the cervix. Cytologist follow up recommendations and the clinicians' response were evaluated. RESULTS: A total of 1196 Pap smears were reviewed. Of the total 510 (42.6%) smears represented group I. Vast majority 506/510 (99.2%) were reported to be normal. A 12 months follow up was given for 505/506 (99.8%) smears. Only 4/510 (0.8%) Pap smears were abnormal and relevant cytologist's recommendations were given. Clinicians reassessed the uterine cervix for only 7.7% of the patients in the group. A total of 686/1196 (57.4%) smears represented group II. The vast majority 630 (91.8%) were with normal cervical appearance, 627/630 (99.5%) had normal cytology and only 3/630 (0.5%) had significant intraepithelial lesion. Relevant recommendations were given by the cytologist and were accepted by clinicians. A total of 56/686 (8.2%) had abnormal cervical appearance and 45/56 (80.4%) had normal cytology. A 12 months follow up was recommended for all except 7/45 (15.6%). Clinicians have followed these recommendations for all except 5/45 (11.1%). Eleven out of 56 (19.6%) smears were abnormal, relevant recommendations were given by the cytologist and all were followed by the clinicians. CONCLUSION: High proportion of cervical smears request did not report clinical appearance of uterine cervix (42.6%). In patients whose cervical smear was reported abnormal (8.2%), 19.6% of them were found with significant intra-epithelial lesion. The clinical appearance of the cervix should be documented on the Pap smear request. Follow up recommendation for Pap smears carried out without clinical appearance description should be left to the clinician.

Cervix Uteri↗
PubMed2005

Polymorphisms of the IL-8 and CXCR2 genes are not associated with Behçet's disease.

OBJECTIVE: Genetic susceptibility to Behçet's disease (BD) is well documented for HLA-B51; however, contribution of other genetic polymorphisms is estimated to be substantial. Interleukin 8 (IL-8), a potent chemoattractant for neutrophils, has been found to be elevated in BD serum, and the serum concentrations correlate with disease activity. Novel polymorphisms in IL-8 (CXCL8) and in one of its receptors, CXCR2 gene, may have a role in enhanced IL-8 activity in BD. METHODS: Three single nucleotide polymorphisms (SNP; -353 A/G, +1530 T/C, +3331 A/G) of the IL-8 gene and 2 SNP (+785 C/T and +1208 T/C) of the CXCR2 gene were screened in 100 patients with BD (61 men, 39 women, mean age 42.1 yrs) and 100 healthy controls (50 men, 50 women, mean age 36.8 yrs) by genotyping with PCR-RFLP and PCR-SSP methods. RESULTS: No differences were observed between BD patients and controls for the allele and genotype frequencies of the screened IL-8 and CXCR2 gene polymorphisms. Distribution of these polymorphisms revealed no significant differences between clinical subgroups of BD patients. Each pair of the SNP -353/+1530, -353/+3331, and +1530/+3331 of IL-8 and +785/+1208 of CXCR2 showed strong linkage disequilibrium in both patients and controls (p < 0.001 for all). The distribution of the estimated IL-8 and CXCR2 haplotypes revealed no association with BD or any of its clinical subsets. CONCLUSION: These results suggest that the IL-8 gene -353 A/G, +1530 T/C, and +3331 A/G and the CXCR2 gene +785 C/T and +1208 T/C polymorphisms have no role in the increased expression of IL-8 in BD.

Adult↗
PubMed2004

Saudi National Guard donor screening for human T cell lymphotropic virus I/II: time to use molecular biology techniques.

Human T cell lymphotropic virus (HTLV) I/II is a retrovirus that is usually transmitted through transfusion of cellular blood products, sexual contact, and vertically from mother to child through breastfeeding. Policies to screen donated blood for this virus have varied from country to country, based on seroepidemiological data. Before 1991, no such data existed on HTLV-I/II among the Saudi population. Since then, several reports have documented a low seroprevalence rate among Saudi blood donors (0-0.026%). We did a retrospective review of all blood donated at King Fahad National Guard Hospital over the preceding 3 years to assess the seroprevalence of HTLV-I/II. After retesting positive and borderline samples, we were able to detect 1 positive and 38 borderline samples. As well, we reviewed the Saudi literature to identify the national seroprevalence of the disease and propose a cost-effective approach for screening donated blood in Saudi Arabia for HTLV-I/II.

Blood Donors↗
PubMed2004

Fc receptor gamma subunit polymorphisms and systemic lupus erythematosus.

OBJECTIVE: To investigate the possible association between Fc receptor (FcR) gamma polymorphisms and systemic lupus erythematosus (SLE). METHODS: We have investigated the full FcR gamma gene for polymorphisms using polymerase chain reaction (PCR)-single strand conformational polymorphism and DNA sequencing. The polymorphisms identified were genotype using PCR-restriction fragment length polymorphism. Systemic lupus erythematosus cases and controls were available from 3 ethnic groups: Turkish, Spanish and Caucasian. The study was conducted in the year 2001 at the Arthritis Research Campaign, Epidemiology Unit, Manchester University Medical School, Manchester, United Kingdom. RESULTS: Five single nucleotide polymorphisms were identified, 2 in the promoter, one in intron 4 and, 2 in the 3' UTR. Four of the 5 single nucleotide polymorphisms (SNPs) were relatively common and investigated in the 3 populations. Allele and genotype frequencies of all 4 investigated SNPs were not statistically different between cases and controls. CONCLUSION: Fc receptor gamma gene does not appear to contribute to SLE susceptibility. The identified polymorphisms may be useful in investigating other diseases where receptors containing the FcR gamma subunit contribute to the pathology.

Alleles↗
PubMed2003

HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis.

PURPOSE: To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction. METHODS: Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1. RESULTS: Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01). CONCLUSION: Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.

Adult↗
PubMed2003

Corticotropin-releasing hormone promoter polymorphisms in patients with rheumatoid arthritis from northwest Spain.

OBJECTIVE: To investigate the possible implications of polymorphism in the CRH promoter in rheumatoid arthritis (RA) susceptibility, we examined a series of patients with RA from a defined area of Northwest Spain. METHODS: A total of 177 patients with RA and 147 ethnically matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for CRH polymorphisms in the 5' regulatory region of the gene at position 1273 (alleles A1 and A2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Patients were stratified for age at onset of disease and rheumatoid factor status. RESULTS: When the whole group of patients was examined, no significant differences in CRH allele or genotype frequency were found compared with controls. However, the CRH allele A2 was significantly increased in patients with late onset seronegative RA compared with the seronegative group with younger age of disease onset (p = 0.03). In addition, 4 (36.4%) of the 11 patients with late onset seronegative RA carried the CRH-A2 allele versus only 2 (6.6%) of 31 patients with seronegative RA beginning before age 61 (OR 8.3, 95% CI 1.4-47.0; p = 0.015). CONCLUSION: In Northwest Spain, polymorphism in the CRH gene regulatory region may play a role as a disease susceptibility marker for late onset seronegative RA.

Age of Onset↗
PubMed2003

Pattern of viral hepatitis infection in a selected population from Saudi Arabia.

Viral hepatitis is an important health problem worldwide. Globally, three major viruses are the leading cause of hepatitis: hepatitis A, B, and C. In this study, we have investigated the pattern of hepatitis among the National Guard personnel and their extended families seen in the central region of Saudi Arabia. The most dominant type of hepatitis infection was hepatitis B virus (HBV), followed by hepatitis C virus (HCV), and to a lesser extent hepatitis A virus (HAV). Our results showed three different age groups at risk of acquiring the infection: HAV, which is mainly a disease of the young; HBV, a disease of adolescents and adults; and HCV, a disease of the elderly. There was no significant difference in the male:female ratio in HAV and HCV; however, as seen in the developed countries, more males were affected with HBV than females. These data will pave the way for further studies by identifying the risk groups for the three major hepatitis infections and by using the data as a preventive tool to educate those risk groups.

Adolescent↗
PubMed2002

Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis.

OBJECTIVE: Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA-DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE. METHODS: The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA-DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi-square tests and logistic regression analysis. RESULTS: Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking. CONCLUSION: Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA-DR-restricted immune response. The association of the SE with RF positivity is primarily due to HLA-DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.

Adult↗
PubMed2002

Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: All human leukocyte antigen (HLA)-DRB1 alleles associated with rheumatoid arthritis (RA) encode a conserved amino acid sequence (QKRAA, QRRAA, or RRRAA) at position 70-74 in the third hypervariable region (HVR3) of the DRbeta(1) chain, which is commonly called the shared epitope (SE). Several studies, however, have associated the HLA-DRB1 gene in RA severity and progression rather than with susceptibility. Moreover, the association with disease severity and presence of the SE varies among different ethnic populations. HLA-DRB1 alleles also influence the disease onset. In this manuscript, the role of the HLA genes in RA was examined. METHODS: A retrospective review of the literature was conducted to analyze the influence of the HLA-class II genes on the susceptibility, severity and protection against RA. RESULTS: The HLA-DRB1*0401/*0404 genotype was associated with a higher risk for early disease onset in more severe forms in patients from the United Kingdom (UK). In northwest Spain, RA onset under 40 years is strongly associated with HLA-DRB1*0401 and *0404. In contrast, RA onset above 60 years is associated with HLA-DRB1*01. The protection against RA linked to some HLA-DRB1 alleles encoding a DERAA sequence of amino acids at position 70-74 in the HVR3 of the DRbeta1 chain, and specifically aspartic acid (D) at position 70 of this chain, recently was confirmed in both UK and northwest Spanish populations. Besides HLA-class II, other genes may be implicated in RA. Polymorphism in the tumor necrosis factor (TNF) region seems to be associated with RA, even in patients without the HLA-DRB1 SE. However, other genes such as interleukin-1 (IL-1) and corticotropin-releasing hormone may play a role in susceptibility to RA. CONCLUSIONS: The additive effect of various genes may account for the development of RA and its clinical severity.

Arthritis, Rheumatoid↗
PubMed2002

Immunophenotyping of peripheral blood lymphocytes in Saudi men.

Flow cytometry is an important tool for the diagnosis and follow-up of immunodeficiency patients, as well as for patients with leukemia and lymphoma. Lymphocytes and their subsets show variations with race. The aim of this study was to establish reference ranges for lymphocytes and their subsets in an Saudi adult population by using flow cytometry. Blood samples obtained from 209 healthy Saudi men were used for this study. All blood donors were between 18 and 44 years old. Lymphocytes and their subsets were analyzed by flow cytometry, and the absolute and percentage values were calculated. We investigated the expression of T-cell markers (CD3, CD4, and CD8), B cells (CD19), and natural killer cells (CD16 and CD56). The absolute and percent values of each cell subset were compared with published data from different populations by using the Student t test. Reference ranges, each expressed as the mean +/- the standard deviation, were as follows: leukocytes (6,335 +/- 1759), total lymphocytes (2,224 +/- 717), CD3 cells (1,618 +/- 547), CD4 cells (869 +/- 310), CD8 cells (615 +/- 278), CD19 cells (230 +/- 130), and CD3-CD16(+)/CD56+ cells (262 +/- 178). The CD4/CD8 ratio was 1.6 +/- 0.7. Our results for B cells, CD4 cells, and CD8 cells and for the CD4/CD8 ratio fell in between the reported results for Ethiopian and Dutch subjects. Our results were also different from previously reported findings in an Saudi adult population that showed no increase in CD8 T cells. We thus establish here the reference ranges for lymphocytes and their subsets in a large cohort of Saudi men. The CD8 cell count was not abnormally high, as previously reported, and fell in between previous results obtained for African and European populations.

Adolescent↗
PubMed2002

Patients chosen for treatment with cyclosporine because of severe rheumatoid arthritis are more likely to carry HLA-DRB1 shared epitope alleles, and have earlier disease onset.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) selected for treatment with cyclosporin A (CSA) because of severe disease are more likely to carry HLA-DRB1 alleles encoding the conserved "shared epitope" (SE) sequence. METHODS: The majority of patients (n = 178) were currently being treated with methotrexate (MTX), either alone or in combination with chloroquine and/or CSA. In about 30% of patients, treatment with CSA had been initiated because of limited response to MTX or MTX and chloroquine. Patients were treated as clinically indicated without knowledge of their HLA-DRB1 status. HLA-DRB1 typing was by a reverse dot blot method. RESULTS: Patients that had been treated with CSA were significantly more likely to carry an SE allele than patients not treated with CSA (81.5% vs 60.5%; OR 2.9, p = 0.006). Patients with 2 SE alleles were the most likely to have been treated with CSA. Results were still significant after correction for age, sex, and disease duration in a logistic regression model. There was no association between rheumatoid factor positivity and requirement for CSA therapy. Examination of individual SE alleles by multiple logistic regression analysis indicated that the strongest association was with presence of HLA-DRB1**0401 (p = 0.004). The DRB1*0401/*0404 genotype provided the greatest risk of requiring CSA treatment. Patients selected for CSA treatment had developed RA at a significantly earlier age than those not requiring CSA (44.4 vs 51.3 yrs; p = 0.004). CONCLUSION: Patients requiring treatment with CSA because of severe RA were significantly more likely to carry an SE allele than patients not requiring such treatment. CSA treated patients were also more likely to have had earlier age of disease onset. These data provide further evidence that bearing the SE (particularly 2 alleles) is associated with development of severe RA.

Adult↗
PubMed2002

Intercellular adhesion molecule-1 gene polymorphisms in isolated polymyalgia rheumatica.

OBJECTIVE: In untreated polymyalgia rheumatica (PMR), high levels of circulating soluble intercellular adhesion molecule-1 (ICAM-1) have been observed. To investigate the clinical implication of ICAM-1 polymorphisms in isolated PMR, we examined their potential influence in an unselected series of patients. METHODS: We studied 72 patients with isolated PMR and 129 ethnically matched controls from Lugo, Spain. Patients and controls were genotyped for HLA-DRB1 and ICAM-1 polymorphism at codons 241 and 469 by molecular methods. RESULTS: The distribution of alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between patients with isolated PMR and controls. There were also no associations between ICAM-1 polymorphisms and relapses of the disease. The latter was primarily associated with carriage of an HLA-DRB1*0401 allele (OR 7.2, p = 0.01), although all relapsed patients with HLA-DRB1*0401 also carried the GG genotype of the ICAM-1 polymorphism at codon 241. The presence of both HLA-DRB1*0401 and the GG241 ICAM-1 genotype gave an OR of 15.2 (p = 0.005) after correction for age and sex. CONCLUSION: Although ICAM-1 polymorphisms alone do not appear to be associated with disease severity in isolated PMR, the presence of both HLA-DRB1*0401 and the ICAM-1 codon 241 GG homozygosity was significantly associated with increased risk of relapses in these patients.

Gene Frequency↗
PubMed2002

Henoch-Schönlein purpura and cutaneous leukocytoclastic angiitis exhibit different HLA-DRB1 associations.

OBJECTIVE: To examine the HLA-DRB1 genotype of patients with cutaneous leukocytoclastic angiitis (CLA), a small-sized blood vessel vasculitis limited to skin, and determine if differences exist with Henoch-Schönlein purpura (HSP), a small-sized blood vessel vasculitis with cutaneous and systemic complications. METHODS: A retrospective study was performed on an unselected population of patients from Northwest Spain with primary cutaneous vasculitis classified according to proposed criteria. Patients who fulfilled classification criteria for hypersensitivity vasculitis were included in this study if they had a biopsy proven leukocytoclastic vasculitis limited to skin and, due to this, they also met the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. Patients were included in this study if they had at least 2 years' followup. We studied 96 Caucasian patients (58 HSP, 38 CLA). Patients and ethnically matched controls (n = 145) were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: No HLA-DRB1 genotype differences between patients with CLA and controls were seen. HLA-DRB1*01 was increased and HLA-DRB1*07 reduced in HSP patients compared to controls. When HLA-DRB1 genotypes of patients with CLA and HSP were compared a significant increase of HLA-DRB1*15/16 and especially of HLA-DRB1*07 was observed in the patients fulfilling definitions for CLA compared to those with HSP. CONCLUSION: HSP and CLA exhibit different HLA-DRB1 genotype associations.

Adult↗
PubMed2002

HLA-B35 association with nephritis in Henoch-Schönlein purpura.

OBJECTIVE: To investigate the implications of the HLA-B locus in the susceptibility to Henoch-Schönlein purpura (HSP) and determine if there are associations with renal and gastrointestinal (GI) manifestations of the disease. METHODS: A retrospective study was performed on an unselected population of patients with HSP from Northwest Spain. Forty-eight Caucasian patients (24 women), 11 of them older than 20 years, were studied. Patients and ethnically matched controls were HLA-B genotyped from DNA using molecular based methods. RESULTS: When patients with HSP were compared with matched controls, no differences in HLA-B frequencies were observed. No HLA-B associations with GI manifestations were observed. In contrast, an increased frequency of HLA-B35 was observed in patients with renal manifestations (10 of 31) compared to those without (0 of 17). No significant distortions in frequency were seen for any other HLA-B alleles with HSP subgroups. CONCLUSION: Our results support a role of HLA-B35 in the susceptibility for nephritis in unselected patients with HSP.

Adult↗
PubMed2002

Interleukin 1 receptor antagonist gene polymorphism is associated with severe renal involvement and renal sequelae in Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of interleukin 1 receptor antagonist gene polymorphism (IL1RN) in the incidence of Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA) and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV) according to proposed criteria were studied. Patients with HV were included if they had a biopsy proven small size blood vessel leukocytoclastic vasculitis limited to skin and also fulfilled the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1 receptor antagonist intron 2 VNTR polymorphism. RESULTS: We examined 96 Caucasian patients (58 HSP and 38 CLA) and 109 controls. No allele or genotype differences between the whole group of HSP or CLA patients and controls were observed. We found a significant association between carriage of IL-1 receptor antagonist allele 2 (ILRN*2) and severe renal involvement, manifested as nephrotic syndrome and/or renal insufficiency (p = 0.016), and permanent renal involvement (renal sequelae) (p = 0.012). CONCLUSION: In unselected patients with cutaneous vasculitis, carriage of ILRN*2 alleles influences disease severity rather than susceptibility.

Adolescent↗
PubMed2002

Macrophage migration inhibitory factor gene polymorphism is associated with sarcoidosis in biopsy proven erythema nodosum.

OBJECTIVE: To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at the position -173 is implicated in the development of sarcoidosis. METHODS: Twenty-eight patients with biopsy proven erythema nodosum (EN) associated with sarcoidosis, 70 patients with biopsy proven EN related to other etiologies, and 122 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for a single nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). RESULTS: A significantly increased frequency of the C mutant allele was observed in patients with EN secondary to sarcoidosis compared to controls (p = 0.0016; p(corr) = 0.0032; OR 2.78, 95% CI 1.45, 5.35) and also compared to patients with EN unrelated to sarcoidosis (p = 0.0004; p(corr) = 0.0008; OR 3.72, 95% CI 1.75, 7.87). Patients with EN carrying an MIF 173 C allele were found to have an increased risk of sarcoidosis (57% in EN secondary to sarcoidosis vs 24% in patients with EN related to other etiologies; p = 0.002; p(corr) = 0.004; OR 4.16, 95% CI 1.64, 10.50). CONCLUSION: This is the first attempt to assess the influence of MIF genetic polymorphism at position -173 in the development of sarcoidosis. The MIF 173 C allele is associated with a significantly increased risk of developing sarcoidosis in patients with EN.

Adolescent↗
PubMed2002

Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLA-DRB1/TNF gene interaction.

OBJECTIVE: To investigate the association of nodular disease in rheumatoid arthritis (RA) with smoking, seropositivity, and polymorphisms at HLA-DRB1 and TNF loci. METHODS: Consecutive patients with RA (n = 420) attending a hospital clinic were examined for the presence of subcutaneous nodules. Rheumatoid factor (RF) status and HLA-DRB1 genotype were determined on every patient, and their smoking history was recorded. TNFa microsatellite polymorphisms were examined in a subgroup of 144 patients. The relationships between smoking, RF status, HLA-DRB1 genotype, TNFa microsatellite polymorphism, and the presence of nodules were examined using chi-square tests and logistic regression analyses. RESULTS: Current smokers were more likely to have nodular disease than those who had never smoked (OR 1.8, 95% CI 1.0-2.9). An association was also found between RF positivity and nodular disease (OR 2.2, 95% CI 1.2-3.8) that remained significant after correction for current smoking. A combination of current smoking and seropositivity increased the risk of nodular disease (OR 3.9, 95% CI 1.7-9.1). Analysis of HLA-DRB1 genotypes in this RA population revealed that only DRB1*0401 homozygotes were associated with nodular disease, and that this was independent of the influence of smoking and seropositivity. Individual TNFa microsatellite alleles were not associated with the presence of nodules, but an interactive effect was found between the TNF a6 allele and homozygosity for DRB1*0401. CONCLUSION: Our data indicate that nodular disease in RA is independently associated with current cigarette smoking, seropositivity, and homozygosity for HLA-DRB1*0401. The latter association involves a possible interaction with the TNF a6 microsatellite allele.

Adult↗