Association of Urotensin II Gene Polymorphism with Disease Pattern in Systemic Sclerosis Patients

Background: Urotensin II (U-II) and its receptor, UT, are widely expressed throughout the body. It is known to be the most potent endogenous vasoconstrictor discovered to date. Its physiological mechanisms are similar in some ways to Endothelin 1 (ET-1). Objective: To investigate the possible association of the polymorphism of UTS2 gene (Thr21Met and Ser89Asn) with the susceptibility to SSc and pattern of disease manifestations in Egyptian patients. Results: We found that the Thr21Met MM genotypes of the UTS2 gene were significantly increased in SSc patients (20%) compared to the control subjects (5%) (p=0.013) There was a significant difference in the MM and NN genotypes in diffuse SSc patients (35.7%, 67.9%) compared to limited SSc patients (6.2%, 25%) (p=0.004, 0.001) .The frequency of the N allele of the UT89 gene polymorphism was significantly higher in the SSc patients (58.3%) than in the control subjects (36.7%) (p=0.001). Significant associations were found between Thr21Met MM and Ser89Asn NN genotypes with pitting scars, digital ischemia, pulmonary hypertension, gastrointestinal manifestations and Anti Scleroderma-70 Antibody. Significant associations were found between Thr21Met M allele with pitting scars, digital ischemia and Anti Scleroderma-70 Antibody, while Ser89Asn N allele showed also in addition a significant association with Raynaud's phenomenon and renal manifestations. Conclusion: The results suggest that UTS2 Thr21Met and Ser89Asn genetic polymorphisms may be important risk factors in the development of SSc susceptibility in the Egyptian population, and an indicator of many disease manifestations such as pulmonary hypertension, severe skin and lung involvement in patients with SSc.