RANTES gene polymorphism in polymyalgia rheumatica, giant cell arteritis and rheumatoid arthritis.

OBJECTIVE: To investigate whether a biallelic polymorphism (A or G) occurring within the promoter region of the RANTES gene (position-403) is associated with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and rheumatoid arthritis (RA). METHODS: A PCR-RFLP method was used to genotype cases and controls for this polymorphism. 3 groups of patients were examined; these comprised GCA patients who did not exhibit features of PMR (n = 30), PMR patients who did not exhibit features of GCA (n = 53) and RA patients (n = 99). All patients and controls (n = 65) originated from the area surrounding Lugo, Galicia, NW Spain. RESULTS: A significant increase in the frequency of allele A was found in PMR patients compared with normal controls. A marginal increase of this allele frequency was observed in RA but not in GCA patients. CONCLUSION: This is the first report of an association of a RANTES gene polymorphisms with PMR and RA. Our data suggest a possible role for of RANTES in the development of both PMR and RA.

Low-molecular-mass endothelial cell-stimulating angiogenic factor in relation to capillary growth induced in rat skeletal muscle by low-frequency electrical stimulation.

The involvement of endothelial cell-stimulating angiogenic factor (ESAF) in capillary growth was studied in adult rat skeletal muscles (tibialis anterior, TA, and extensor digitorum longus, EDL) in which capillary growth was induced by chronic unilateral electrical stimulation (10 Hz, 8 h/day for 7 days), and in sham-operated and unoperated control muscles. ESAF was assayed by its ability to activate latent collagenase in units per hour per milligram protein. Anatomical capillary density (CD, number of capillaries per mm2) and capillary per fibre ratio (C/F) were estimated in frozen sections from the same muscles after staining for endothelial alkaline phosphatase. In control muscles, ESAF levels were inversely related to capillary supply, being highest (1.82 +/- 0.25 units) in the glycolytic cortex of TA (CD 273 +/- 18/mm2, C/F 1.26 +/- 0.07), lowest (1.04 +/- 0.02 units) in its oxidative highly capillarized core (CD 862 +/- 60/mm2, C/F 2.05 +/- 0.04), and intermediate in EDL (ESAF 1.59 +/- 0.37 units, CD 527 +/- 26/mm2, C/F 1.44 +/- 0.06). Neither capillary supply nor ESAF levels were affected by sham operation. However, chronic electrical stimulation increased capillary supply significantly in EDL (CD 61% greater than in controls, C/F 45% greater) and ESAF levels were elevated 3-fold to 4.77 +/- 0.74 units. In TA muscles, stimulation increased capillary supply specifically in the glycolytic cortex (C/F 2.51 +/- 0.09, p < 0.0001 vs. control) and ESAF levels were increased significantly in this region to 3.19 +/- 0.55 units (p < 0.05, vs. control). C/F ratio and ESAF in the oxidative core of TA (2.31 +/- 0.05 and 1.48 +/- 0.23 units, respectively) were not significantly different from control values. Thus, chronic electrical stimulation, which is known to increase both shear stress and wall tension in capillaries and induce angiogenesis, also increased ESAF activity.

CTLA-4 gene polymorphism and its association with Graves' disease in the Lebanese population.

Graves' disease is an organ-specific autoimmune disease that has a female predominance. It is probably the result of a complex interaction of genetic and environmental factors. This disease is characterized by immune system activation, evidenced by elevated serum thyroid-specific autoantibodies and lymphocytic infiltration of the target organ (the thyroid gland), associated with raised levels of circulating activated T lymphocytes. Several reports have demonstrated genetic linkage and association between the genetic markers of the CTLA-4 gene on chromosome 2q33 and Graves' disease. In order to confirm this association in the Lebanese population, a bi-allelic A/G polymorphism at position 49 of CTLA-4 exon 1 was studied in 34 patients with Graves' disease, and in 38 healthy individuals, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results showed a significant increase in allele and genotype frequencies in patients with Graves' disease compared to controls. This suggests that the CTLA-4 gene might play a role in the development of Graves' disease in the Lebanese population.

Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients.

The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. RA patients (n=179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n=145) were recruited. RA susceptibility in this population was predominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04. The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner. Logistic regression analyses revealed that the TNF microsatellite markers TNFc1 and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF c1 allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals. TNFc1 and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFc1) polymorphism seemingly associated with low TNFalpha production, is a risk factor for RA.