Lack of association between RETN rs1862513 polymorphism and cardiovascular disease in rheumatoid arthritis patients.

OBJECTIVES: To assess the influence of the RETN rs1862513 polymorphism in the risk of cardiovascular (CV) disease and subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Six hundred and sixty-eight patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, were studied. Patients were genotyped for the RETN rs1862513 polymorphism using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Carotid intima-media thickness (IMT), flow-mediated endothelium-dependent and endothelium independent vasodilatation, used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients. RESULTS: No significant differences in the genotypic or in the allelic distribution between RA patients with or without CV disease were found. In this regard, we only observed a slight increased frequency of homozygous and heterozygous for the minor allele G (CG+GG genotypes) among patients who experienced CV events compared to those without CV events (53.04% vs. 52.62%, p=0.94). A higher frequency of classic CV risk factors was observed among the carriers of the minor allele G. However, in the adjusted logistic regression model no association between the RETN variant and CV disease was found (p=0.50). Also, when surrogate markers of subclinical atherosclerosis were assessed, in the adjusted ANCOVA model only a trend towards a higher carotid IMT was found among allele G carriers (p=0.06). CONCLUSIONS: RETN rs1862513 polymorphism does not seem to be a genetic risk factor for both clinically evident CV disease and subclinical atherosclerosis in patients with RA.

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 of a functional -94ins/delATTG NFKB1 promoter polymorphism with susceptibility and clinical expression of biopsy-proven giant cell arteritis in northwest Spain.

OBJECTIVE: Giant cell arteritis (GCA) is a vasculitis preferentially involving large and middle-sized arteries in the elderly. The nuclear factor of k-light polypeptide gene enhancer in B cells (NF-kB) is a family of 5 proteins expressed in most cells that function to regulate gene transcription. NFKB1 gene plays a critical role in the coordination of the immune system by regulating the transcription of a broad variety of genes implicated in the immune response. A NFKB1 promoter polymorphism consisting of a common insertion/deletion (-94ins/delATTG) located between 2 putative key promoter regulatory elements and showing functional effects on the transcription of the NFKB1 gene has been described. Since GCA is a polygenic disease, we sought to assess the potential role of the -94ins/delATTG NFKB1 promoter polymorphism in susceptibility to GCA and to determine if this polymorphism is implicated in the clinical expression of this vasculitis. METHODS: Ninety-six patients with biopsy-proven GCA and 204 ethnically matched Caucasian controls from the Lugo region (Northwest Spain) were studied. Genotyping of the -94ins/delATTG NFKB1 promoter polymorphism was performed by fluorescent polymerase chain reaction (PCR). RESULTS: No significant differences in allele or genotype frequencies for this NFKB1 promoter polymorphism were observed between patients with GCA and controls even when patients were stratified according to gender, presence of polymyalgia rheumatica (n = 38), severe ischemic manifestations (n = 49), or other clinical manifestations of GCA. CONCLUSION: Our results do not support a role for -94ins/delATTG NFKB1 promoter polymorphism in susceptibility and clinical expression of GCA in a Northwestern Spanish population.