The Renin - Angiotensin System Gene Polymorphisms and Clinicopathological Correlations in lgA Nephropathy
SOMPONG ONG-AJYOOTH, M.Sc.*, APINAN LIMMONGKON, M.Sc.*, PAISAL PARICHATIKANON, M.D.***, LEENA ONG-AJYOOTH, M.D.**, ANCHALEE TIENSINGH, M.D.**, SANGA NILWARANGKUR, M.D.**
Affiliation : * Department of Biochemistry, ** Department of Medicine, *** Department of Pathology. Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok I 0700. Thailand.
Genetic variability in the renin-angiotensin system (RAS) may modify renal responses to injury and disease progression. We examined whether RAS alleles affect severity of IgA nephropathy. These genetic variants include angiotensin I converting enzyme deletion poly- morphism in intron 16 (ACE liD), a point mutation in the angiotensinogen (AGT) gene resulting in a methionine to threonine substitution at residue 235 (M235T) and an angiotensin receptor type I (ATR) A to C transition at bp 1166 (A 1166 C). A total of 53 patients with biopsy-proven IgA nephropathy and 80 normal control subjects were recruited for study. These patients were classified into two groups according to serum creatinine at renal biopsy. Group I patients (n = 40) had normal renal function, serum creatinine ::; 1.5 mg/dl and group 2 patients ( n = 13) had renal insufficiency with serum creatinine > 1.5 mg/dl. The blood pressure and urinary protein of group 2 patients were higher than group 1 (p < 0.01). The mean scores of histological parameters including mesangial proliferation, glomerular sclerosis (global and segmental), the interstitial fibrosis and crescent formation in group 2 patients were significantly higher than in group I patients (p < 0.05). The most frequent genotype in IgA patients was ID (47%) genotype, followed by II (45%) and DD (8%) genotype of ACE gene. The mean serum ACE activity in the DD group was significantly higher than in the II group (p < 0.05) but was not significantly different from that of the ID group. No statistically significant differences were found with respect to allele frequencies between IgA group I, group 2, or between controls and all IgA patients. Furthermore, no significant difference in AGT alleles, ATR alleles frequencies was detected between groups of IgA patients, although a trend for a higher frequency of DO genotype and AGT-TT genotype were noted in lgA group 2. The combined analysis of the ACE-DO and AGT-TT genotypes did not show any genetic influence on the risk of the disease susceptibility. To resolve the true role of ACE genotype and any dependent effect on progression, larger collaborative studies are required.
Keywords : RAS Gene Polymorphism, IgA Nephropathy, Clinicopathology
