Μελέτη του πολυμορφισμού στο ιντρόνιο 4 του γονιδίου της ενδοθηλιακής ισομορφής στης συνθετάσης του μονοξειδίου του αζώτου (ENOS) σε ασθενείς με συστηματικό ερυθηματώδη λύκο και ρευματοειδή αρθρίτιδα στην Κρήτη

Nitric oxide (NO), a short-lived gaseous free radical, synthesized from L-arginine by NO synthases (NOS), has been characterized as a potent mediator of autoimmune and inflammatory responses, thus considered as an agent playing a key role in the pathogenesis of autoimmune diseases. Low concentrations of the intercellular messenger NO are important to endothelial function. Moreover, it directly inhibits platelet aggregation, may compromise coagulation, immune function, control of volume and electrolyte content of the intravascular and extravascular spaces. Most biological NO is produced by the family of three nitric oxide synthases (NOS). In systemic lupus erythematosus (SLE), endothelial nitric oxide synthase (eNOS) gene locus has been found in genetic linkage with the disease; eNOS is produced in significant amounts and endothelial cell dysfunction has been observed. Similarly, several lines of evidence indicate that nitric oxide (NO) may be important in the pathogenesis of rheumatoid arthritis (RA). Upon now, several functionally relevant genetic polymorphisms in the eNOS gene have been associated with different vascular, infectious and autoimmune disease such as SLE and RA in some populations. The objective of this study was to investigate the influence of the eNOS gene intron 4 a/b VNTR polymorphism (a 27 base-pair tandem repeat based polymorphism) on susceptibility to SLE and RA in patients living in the island of Crete, a genetically homogeneous population. A group of 145 healthy subjects and 190 SLE patients were included in this study. Similarly, a second group of 235 healthy controls and 202 RA patients were analyzed. In both cases, patients and controls were sex and age matched. The present study, constituting the first attempt to access the implication of eNOS gene intron 4 a/b polymorphism in susceptibility to SLE and RA in natives of Crete, which share a common genetic and cultural background, has been revealed that the presence of a/b genotype of the eNOS gene may act as a risk factor for the development of RA in island of Crete. In contrast, the same eNOS polymorphism seems to not be associated with susceptibility to SLE