Association between polymorphisms of the renin-angiotensin system and more severe histological forms of lupus nephritis.

Aims: The pathogenesis of lupus nephritis (LN) has not been fully understood. The renin-angiotensin system (RAS) is implicated in various immunological and non-immunological phenomena, and the polymorphism of the RAS genes has been associated with cardiovascular and renal disease onset and outcome. Therefore, we evaluated the possible association between the polymorphism of the renin-angiotensin system genes and the development of the different types of histological lesions of lupus nephritis in Brazilian patients.

Methods: 72 LN patients and 65 healthy subjects (sex-and ethnic-matched) were enrolled and compared in this study. Following the extraction of genomic DNA from the leukocytes of the peripheral blood, the genotypes of the angiotensin converting enzyme (ACE I/D), of the angiotensinogen (AGT M235T) and of the angiotensin II type 1 receptor (AGTR1 A1166C) were determined by the polymerase chain reaction. The renal lesions of the patients with LN were classified by the histological findings according to the WHO criteria. In addition, the activity and chronicity indices were used to assess the severity of renal involvement.

Results: Among the 72 patients with LN, there were 17 class II, 8 class III, 40 class IV and 7 class V, according to the WHO criteria. Individuals with the III and IV classes of LN (WHO) showed a significantly increased DD genotype frequency of ACE I/D genes when compared to the control group (48% vs. 27.7%, chi2 = 4.885, df = 1, p = 0.0442). No difference was found in the distribution of the AGT M235T and AGTR1 A1166C genotype frequencies among the LN of the different histological classes (WHO) and healthy controls. There was no association between genetic polymorphism of ACE, AGT M235T and AGTR1 A1166C and susceptibility to lupus nephritis, nor histological activity and chronicity indices in renal biopsy among the patients studied.

Conclusions: This study suggests that the DD genotype of the ACE may be associated with the development of the more severe histological forms of lupus nephritis.