Role of rs1343151 IL23R and rs3790567 IL12RB2 polymorphisms in biopsy-proven giant cell arteritis.

OBJECTIVE: To assess the potential association between the rs1343151 IL23R and the rs3790567 IL12RB2 polymorphisms and giant cell arteritis (GCA). We also studied whether these polymorphisms might influence the phenotypic expression of GCA. METHODS: In total, 357 Spanish patients with biopsy-proven GCA and 574 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the rs1343151 IL23R and the rs3790567 IL12RB2 polymorphisms using a predesigned TaqMan allele discrimination assay and by polymerase chain reaction amplification. RESULTS: Regarding the rs1343151 IL23R polymorphism, no significant differences in the genotype or allele frequencies between GCA patients and healthy controls were observed. The frequency of the minor allele A of the rs3790567 IL12RB2 variant was increased in GCA patients compared with controls (30.1% vs 25.7%, respectively; p = 0.039, OR 1.25, 95% CI 1.01-1.54). An increased frequency of subjects carrying the minor allele A (GA+AA genotypes) of the rs3790567 IL12RB2 polymorphism was found among GCA patients compared with controls (52.8% vs 44.4%; p = 0.013, OR 1.40, 95% CI 1.06-1.85). Although a higher frequency of the combination of minor alleles (A-A) in the subgroup of patients with visual ischemic complications compared with the combination of both major alleles (G-G; p = 0.029) or with the other allelic combinations (p = 0.035) was found, logistic regression analysis showed that this association was no longer significant after adjustment for potential confounding factors (A-A vs G-G: OR 2.10, 95% CI 0.88-5.04, p = 0.096). CONCLUSION: Our results support a potential influence of the rs3790567 IL12RB2 polymorphism in the pathogenesis of GCA.

Role of the rs6822844 gene polymorphism at the IL2-IL21 region in biopsy-proven giant cell arteritis.

OBJECTIVES: To assess the influence of the interleukin (IL)2-IL21 rs6822844 G/T polymorphism in the susceptibility to biopsy-proven giant cell arteritis (GCA) and in the clinical spectrum of manifestations of this vasculitis. METHODS: Two hundred and seventy-two biopsy-proven GCA patients were included in this study. DNA from patients and matched controls (n=791) was obtained from peripheral blood. Samples were genotyped for the rs6822844 polymorphism using a predesigned TaqMan allele discrimination assay and by polymerase chain reaction amplification. RESULTS: No significant differences in the allele and genotype frequencies between biopsy-proven GCA patients and controls were observed. However, the stratification of GCA patients disclosed some differences according to gender and ischemic manifestations of the disease. In this regard, the frequency of the minor allele T was increased in males (14.8%) compared to females (8.4%) (odds ratio-OR:1.89 (95% confidence interval-CI: 1.09-3.28); p=0.02; Bonferroni adjustment p=0.12). Also, minor allele T frequency was increased in GCA patients with severe ischemic complications (12.8%) compared to those without severe ischemic complications (7.7%) (OR:1.72 (95% CI: 0.97-3.05); p=0.05; Bonferroni adjustment p=0.30), and specifically in patients with jaw claudication (13.7% versus 8.2% in those without jaw claudication; OR:1.76 (95% CI: 1.02-3.04); p=0.04; Bonferroni adjustment p=0.24). CONCLUSIONS: IL2-IL21 rs6822844 polymorphism does not appear to be a genetic risk factor for susceptibility to biopsy-proven GCA. However, this gene polymorphism may contribute to the different phenotypic expression of this vasculitis, in particular in the development of ischemic complications of the disease.

Role of BANK1 gene polymorphisms in biopsy-proven giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is a complex polygenic disease in which more than 1 genetic locus is likely to contribute to disease susceptibility and clinical expression. BANK, an adaptor molecule, has been suggested to participate in the B cell antigen receptors-mediated calcium homeostasis. We assessed for the first time the implication of BANK1 functional variants in susceptibility to GCA. METHODS: Two hundred twenty-two patients with biopsy-proven GCA and 534 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for 3 putative functional BANK1 gene polymorphisms (rs17266594 T/C, rs10516487 G/A, rs3733197 G/A) using a TaqMan allele discrimination assay. RESULTS: No significant differences were observed in genotype distribution between patients with biopsy-proven GCA and controls for these 3 gene polymorphisms. A trend for a decreased risk of having GCA was observed in individuals carrying the BANK1 rs3733197 GG genotype (patients with GCA 43.9% compared to 51.6% in controls; p = 0.06, OR 0.73, 95% CI 0.53-1.02). The frequency of BANK1 rs3733197 allele G was marginally decreased in patients with biopsy-proven GCA compared to controls (p = 0.09, OR 0.82, 95% CI 0.64-1.04). Haplotype analysis of 3-single-nucleotide polymorphisms found no statistically significant differences between patients with GCA and controls. No significant differences for the BANK1 gene polymorphisms were found when patients were stratified according to specific clinical features of the disease. CONCLUSION: Our results do not support a major implication of the BANK1 locus in susceptibility to GCA.

Lack of association between IFNGR1 gene polymorphisms and biopsy-proven giant cell arteritis.

OBJECTIVES: Since IFN-gamma plays a pivotal role in the pathogenesis of giant cell arteritis (GCA), a polygenic primary systemic vasculitis involving elderly people from Western countries, in the present study we analysed for first time the implication of three IFN-gamma receptor (IFNGR) 1 gene variants in the susceptibility to and clinical expression of GCA. METHODS: Two hundred and sixteen biopsy-proven GCA patients and 460 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for three single nucleotide polymorphisms (SNPs) rs1327474 (-611A/G), rs11914 (+189G7C) and rs7749390 (+95C/T) of the IFNGR1 gene using a pre-designed TaqMan allele discrimination assay. Post PCR, the genotype of each sample was attributed automatically by measuring the allelic specific fluorescence on the ABI PRISM 7900 sequence. RESULTS: No significant differences in the genotype or allele distribution between GCA patients and controls for the three IFNGR1 gene variants were found. Furthermore, no significant differences in the genotype distribution were observed when GCA patients were stratified according to the presence of specific clinical features of the disease such as polymyalgia rheumatica or severe ischemic complications including visual ischemic manifestations. CONCLUSIONS: Our results do not show an implication of IFNGR1gene polymorphisms in the susceptibility to and clinical expression of GCA.

Lack of association between hypoxia inducible factor-1 alpha gene polymorphisms and biopsy-proven giant cell arteritis.

OBJECTIVES: Since the transcription factor hypoxia-inducible factor 1 (HIF-1) is a key early mediator of the response to ischemia and giant cell arteritis (GCA) is a polygenic disease leading to severe ischemic complications, in the present study we analysed for first time the implication of two HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA. METHODS: Two hundred and fifteen biopsy-proven GCA patients and 470 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for two single nucleotide polymorphisms, rs11549465 (C/T) and rs11549467 (G/A), using a pre-designed TaqMan allele discrimination assay. Post PCR, the genotype of each sample was attributed automatically by measuring the allelic specific fluorescence on the ABI PRIM 7900 sequence. RESULTS: The HIF-1alpha, rs11549465 TT genotype was extremely uncommon in both GCA patients (2.3%) and controls (2.1%). Although the frequency of individuals carrying the CT or TT genotypes was increased in GCA patients (25.1%) compared to controls (20.4%) the difference was not statistically significant (OR 1.30 [95% CI: 0.89- 1.91]; p=0.17). Also, all GCA patients and most controls (98.9%) were homozygous for the rs11549467 GG genotype. GCA patients carrying the rs11549465 CT or TT genotypes had a slight increased risk of developing visual ischemic complications (33.1%) compared to the remaining GCA patients (22.8%); OR 1.60 (95% CI: 0.81- 3.16); p=0.18. CONCLUSIONS: Our results do not confirm an implication of HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA.

Lack of association between the rs6920220 (G/A) polymorphism of the 6q23 region and biopsy-proven giant cell arteritis.

OBJECTIVE: Recently, 2 independent studies have identified an association between several single-nucleotide polymorphisms (SNP) located in the 6q23 chromosomal region and rheumatoid arthritis (RA). Like RA, giant cell arteritis (GCA) is also a complex polygenic disease in which more than 1 genetic locus is likely to contribute to disease susceptibility and clinical expression. We analyzed the involvement of the rs6920220 (G/A) polymorphism from the 6q23/TNFAIP3 gene region in susceptibility to GCA. METHODS: Two hundred twenty patients with biopsy-proven GCA and 490 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were geno-typed for the 6q23 region rs6920220 using a TaqMan allele discrimination assay and by polymerase chain reaction (PCR) amplification. After PCR, the genotype of each sample was attributed automatically by allelic-specific fluorescence using the ABI Prism 7900 sequence detection system. RESULTS: No significant differences in the genotype distribution between patients with GCA and controls for the rs6920220 (G/A) polymorphism were found. No significant differences were observed when patients with GCA were stratified according to the presence of specific clinical features of the disease such as polymyalgia rheumatica or severe ischemic manifestations or specific visual ischemic complications. CONCLUSION: Our results show no involvement of this 6q23/TNFAIP3 gene region SNP in the susceptibility to or clinical expression of GCA.

High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors.

OBJECTIVE: To assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) without clinically evident atherosclerosis or its complications, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease in a series of patients with PsA attended to in a community hospital. METHODS: Fifty-nine patients with PsA who fulfilled the Moll and Wright criteria were recruited from Hospital Xeral-Calde (Lugo, Spain). Patients seen during the period of recruitment who had classic cardiovascular risk factors or had experienced cardiovascular or cerebrovascular events were excluded. Fifty-nine healthy matched controls were also studied. Carotid artery intima-media thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound. RESULTS: Patients with PsA exhibited greater carotid artery IMT than did matched controls (mean +/- SD 0.699 +/- 0.165 mm versus 0.643 +/- 0.111 mm; P = 0.031; difference of means 0.056; 95% confidence interval 0.005-0.108). Adjusted for age, the carotid IMT was correlated with age at the time of PsA diagnosis (partial correlation coefficient [r] = -0.264, P = 0.04), disease duration (r = 0.264, P = 0.04), total cholesterol (r = 0.233, P = 0.01), and low-density lipoprotein cholesterol (r = 0.243, P = 0.01). CONCLUSION: The present study demonstrates that patients with PsA without cardiovascular risk factors or clinically evident cardiovascular disease have a high prevalence of macrovascular disease in the form of increased carotid artery IMT compared with ethnically matched controls.

Endothelial dysfunction in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors.

OBJECTIVE: To determine whether endothelial dysfunction was present in a cohort of patients with psoriatic arthritis (PsA) without overt cardiovascular disease or classic cardiovascular risk factors attended to in a community hospital. METHODS: Fifty patients with PsA who fulfilled the Moll and Wright criteria were recruited from Hospital Xeral-Calde (Lugo, Spain). Patients seen during the period of recruitment who had classic cardiovascular risk factors or had experienced cardiovascular or cerebrovascular events were excluded. Fifty healthy matched controls were also studied. In all patients and controls, endothelial function was determined by measuring flow-mediated endothelial dependent vasodilatation (FMD%) and endothelial independent vasodilatation (GTN%) by brachial ultrasonography. RESULTS: FMD% was significantly impaired in patients compared with controls (mean, median [range] 6.3%, 6.1% [0.3-13.4%] versus 8.2%, 8.2% [0.0-21.2%]; P = 0.008). However, no significant difference existed between patients and controls in GTN% or baseline diameter. A significant correlation between C-reactive protein level and erythrocyte sedimentation rate at the time of disease diagnosis and FMD% was found (P < 0.04). No significant FMD% and GTN% differences were observed when patients with PsA with polyarticular pattern were compared with the remaining patients with PsA. CONCLUSION: The present study demonstrates that patients with PsA without cardiovascular risk factors or clinically evident cardiovascular disease also exhibit endothelial dysfunction. These observations provide a basis for the potential association between PsA and atherosclerotic disease.

Lack of echocardiographic and Doppler abnormalities in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors.

OBJECTIVE: To assess the prevalence of echocardiographic and Doppler abnormalities in psoriatic arthritis (PsA) patients without clinically evident cardiovascular manifestations or classic atherosclerosis risk factors. METHODS: Fifty PsA patients were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients seen during the period of recruitment that had classic cardiovascular risk factors or had suffered cardiovascular or cerebrovascular events were excluded. Fifty healthy matched controls were also studied. Echocardiographic and Doppler studies were performed in all cases and controls. RESULTS: In PsA patients the frequency of aortic and tricuspid (10%) and mitral regurgitation (16%) was not different from that seen in matched controls (10, 4, and 12%). Also, the pulmonary artery systolic pressure was normal in the group of PsA patients (23.4+/-3.9 mm Hg). The prevalence of diastolic dysfunction, in all cases due to impaired relaxation, was similar in PsA patients (28%) and controls (24%) (P=0.65). In addition, no significant echocardiographic and Doppler differences were observed when PsA patients with polyarticular pattern were compared with the remaining PsA patients. CONCLUSIONS: The present study shows that actively treated PsA patients without cardiovascular risk factors or clinically evident cardiovascular disease do not exhibit silent subclinical echocardiographic abnormalities.