Genetic polymorphisms of the renin-angiotensin system: role in patients with sarcoidosis

Abstract

Introduction: An important component of renin-angiotensin system (RAS) angiotensin-converting enzyme (ACE) is produced by macrophages in sarcoid granulomas. The role of RAS in sarcoidosis pathogenesis is still unclear. Aim: to assess the role of RAS genes polymorphism in patients with chronic sarcoidosis. Methods: Gene polymorphisms ACE I/D, angiotensinogen (AGT) T704C, angiotensin II receptor type 1 (AGTR1) A1166C and type 2 (AGTR2) G1675A were investigated by polymerase chain reaction (PCR) in 142 Caucasian patients with chronic sarcoidosis (CS) and in 35 healthy volunteers (HV). Results:AC genotype AGTR1 is significantly more frequent in patients with CS than in HV: 29% vs 5% p=0,026,OR=7,364,90%CI 1,3-41,7). The difference between frequency of other genotypes was not significant. In patients with CS there are significant (p<0,05) associations between:\n –CC genotype AGT 704 and the onset age, higher occurrence of coughing, Lofgren syndrome, bone lesions, –AA genotype AGTR1 1166 and higher rate of dyspnea, chest pain, serological inflammatory changes at onset, liver involvement, –AC genotype AGTR1 1166 and higher forced vital capacity (FVC), skin involvement, –GA genotype AGTR21675 and female gender, onset age, higher occurrence of cough, higher FVC, erythrocyte sedimentation rate (ESR), –AA genotype AGTR21675 and liver involvement, –DD genotype ACE and higher frequency of asymptomatic disease course, cough, lower kidney function, –II genotype ACE and higher rate of eye involvement, lower FVC. Conclusion: The heterozygous ATR1 A1166C genotype AC is associated with higher sarcoidosis risk. There are significant associations between the RAS genes polymorphism and the clinical features of sarcoidosis.