Naslov
Angiotenzin converting enzyme(ACE)gene polymorphism and lupus nephritis

Autori
Bosnić, Dubravka ; Harjaček, Miroslav ; Sertić, Jadranka ; Čikeš, Nada ; Sentić, Mirna ; Anić, Branimir, Šćukanec-Špoljar, Mira

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Proceedings of XXXth Memorial meeting for Professor Janez Plečnik / International editorial board - Ljubljana : Medicinska fakulteta v Ljubljani, 1999

Skup
XXXth Memorial meeting for Professor Janez Plečnik - Autoimmune systemic diseases

Mjesto i datum
Ljubljana, Slovenija, 02.12.1999. - 03.12.1999

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Lupus nephritis; ACE gene polymorphism

Sažetak
Clinical renal involvement occurs in 40-70% of systemic lupus erythematosus(SLE)patients, and lupus nephritis has one of the most unsatisfactory outcomes of any lupus subsets.SLE is a polygenic trait with complex contributions from MHC and multiple non-MHC genes.The angiotensin-converting enzyme(ACE)is a key component of the renin-angiotensin system, which is likely to be important in the progression of renal diseases because of its effect on tissue hemodynamics and glomerular cell function.Recently, the ACE polymorphism has been implicated in the pathogenesis of a variety disorders, including myocardial infarction, hypertension, IgA and diabetic nephropathy ; there is evidence of the possible role of ACE gene polymorphism in the progression of primary glomerular disease, with significant improvement of renal survival in II homozygotes and a more rapid deterioration of renal function in DD homozygotes.In the present study we investigated whether these observations could be extended to SLE patients with or without renal disease. A total of 79 SLE patients(10 children and 69 adults)and 80 healthy controls were studied.All patients fulfilled at least for of the revised 1997 ACR classification criteria for SLE.Clinical information was collected retrospectively from medical records and included age at presentation, sex, duration of the follow up, medications, systemic involvement and clinical renal disease.Molecular analysis of the ACE genotype was performed by selective amplification of the polymorphic region in intron 16 of the ACE gene(Alu repetitive sequence)by polymerase chain reaction(PCR)and gel electrophoresis.Data were expressed as means and standard deviation.The X2 test was used to compare genotype frequency between groups.Significance was defined as p<0.05. The genotype distribution in the SLE patients group was 44 DD(55.7%), 18 ID(22.8%)and 17 II(21.5%) ; (p<0.00054). In the control group the genotype distribution was 21 DD(25.5%), 36 ID(47%) and II 23(27.5%) ; (p<0.00054).In patients with clinical renal disease, the genotype distribution was DD 20, ID 7, and II 8 compared with respective values of DD 24, ID 11, and II 9 in the group not developing renal disease(p<0.822).The records of renal biopsies were available in 12 SLE patients.In this study, we have found a significantly increased frequency of the DD ACE genotype(p<0.00054)in SLE patients, when compared to healthy controls.The reason for this association might represent the role of increased in situ angiotensin II activity in vascular changes observed in SLE patients(e.g.accelerated atherosclerosis, vasculitis, etc.).Alternatively, the ACE genes are just localized close to a "true" candidate gene(s)on human chromosome 18.We demonstrated no association between ACE D/I polymorphism with onset or progression of the clinical renal disease in SLE patients.Interestingly, in a very limited number of our SLE patients DD genotype was associated with diffuse proliferative glomerulonephritis.A lack of association between DD genotype and clinical renal disease in SLE patients does not negate a possible contribution of angiotensin in its pathophysiology.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA