ABSTRACT
OBJECTIVES: Bacteria have long been suggested as aetiological factors in the genetically susceptible host in spondylarthropathies, including ankylosing spondylitis (AS) and reactive arthritis (ReA). Variability of the Toll-like receptor 4 (TLR4) gene has been shown to play a role in the inflammatory response to certain bacterial infections. We investigated whether TLR4 Asp299Gly and Thr399Ile polymorphisms contribute to the genetic background of spondylarthropathies in a cohort of Hungarian patients with AS and ReA. METHODS: DNA was obtained from patients with AS (n=138), ReA (n=91) and ethnically matched healthy controls (n=140). Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism analysis and the results were confirmed by direct sequencing. RESULTS: No significant differences in allele or genotype frequencies were observed between controls and either the AS patients or the ReA patients. Clinical characteristics of these groups were unrelated to the presence of any of these polymorphisms. CONCLUSIONS: Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms do not contribute to disease susceptibility in either AS or ReA. Functional abnormalities of the TLR4 signalling pathway suggested in spondylarthropathies seem not to be genetically determined by these two common polymorphisms.
Subject(s)
Arthritis, Reactive/genetics , Polymorphism, Genetic , Spondylitis, Ankylosing/genetics , Toll-Like Receptor 4/genetics , Adult , Case-Control Studies , Chi-Square Distribution , Female , Gene Frequency , Genetics, Population , Genotype , Humans , Hungary , Linkage Disequilibrium , Male , Middle Aged , Polymerase Chain Reaction/methods , Polymorphism, Restriction Fragment Length , ProhibitinsABSTRACT
The actions of ovariectomy on nitric oxide synthase (assessed by the citrullin assay), mucus secretion (assessed by the Alcyan blue technique) and ulcerogenic response (indomethacin (30 mg kg(-1), s.c. , 4 h) or cysteamine (400 mg kg(-1), s.c., 24 h)) were studied in the female rat stomach. Ovariectomy increased nitric oxide synthase and mucus secretion, and decreased the severity of lesions, effects reversed by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg kg(-1), s.c., 4 h before measurements). Therefore, estrogen-deficiency protects the gastric mucosa by nitric oxide (NO)-mediated mucus hypersecretion.
