PMID- 14767013
OWN - NLM
STAT- MEDLINE
DCOM- 20040713
LR  - 20190513
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 19
IP  - 3
DP  - 2004 Mar
TI  - Interaction between gene polymorphisms of nitric oxide synthase and 
      renin-angiotensin system in the progression of membranous glomerulonephritis.
PG  - 587-95
AB  - BACKGROUND: The renin-angiotensin system (RAS) and nitric oxide synthase (NOS) 
      play a key role in the progression of primary glomerulonephritis (GN). Although 
      previous studies have examined genetic risk associated with single gene 
      variations, experiments assessing risk conferred by multiple gene variations are 
      still scanty. METHODS: The effect of combination of variant alleles of four genes 
      encoding for three components of the RAS [angiotensin converting enzyme 
      insertion/deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), 
      angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and 
      progression of membranous GN (MGN) were evaluated in a longitudinal study 
      comparing 117 patients with serum creatinine (s-Cr) <1.5 mg/dl at renal biopsy 
      and follow-up > or = 5 years (Kaplan-Meier and Cox multivariate analysis). The 
      control group consisted of DNA from 171 organ donors. RESULTS: We found no 
      relationship between single or combined variations of the four gene polymorphisms 
      and development of MGN. Among single gene variations, there were no independent 
      genetic risk factors for the progression of renal disease, after adjustment for 
      age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. 
      However, double variation coincidences such as the combination of the allele a of 
      ecNOS4b/a and both the allele D of ACE I/D (chi(2) =4.80, P = 0.028; HR = 1.97, 
      95% CI 0.98-3.96) and the allele T of AGT (M235T) (chi(2) = 5.09, P = 0.024; HR = 
      2.84, 95% CI 1.39-5.82) exerted an additional effect that was higher than that of 
      the single gene variations. CONCLUSION: This study is the first to demonstrate a 
      role for an interaction between simultaneous variations of genes encoding for NOS 
      and components of RAS in the progression of MGN. Interactions between various 
      polymorphisms may explain conflicting results obtained in previous studies that 
      examined single gene variations, since the effect of a single locus variation may 
      be influenced by the simultaneous presence of other variant alleles in polygenic 
      diseases such as primary GN. However, the small sample sizes and possible 
      multiple interactions limited the interpretation of the current findings, which 
      may represent true biological interaction or simply statistical interactions or 
      spurious results due to the small sample sizes.
FAU - Stratta, Piero
AU  - Stratta P
AD  - Department of Internal Medicine, Section Nephrology, S.Giovanni-Molinette 
      Hospital, Torino, Italy. estrattanefro@hotmail.com
FAU - Bermond, Francesca
AU  - Bermond F
FAU - Guarrera, Simonetta
AU  - Guarrera S
FAU - Canavese, Caterina
AU  - Canavese C
FAU - Carturan, Sonia
AU  - Carturan S
FAU - Dall'Omo, Annamaria
AU  - Dall'Omo A
FAU - Ciccone, Giovannino
AU  - Ciccone G
FAU - Bertola, Laura
AU  - Bertola L
FAU - Mazzola, Gina
AU  - Mazzola G
FAU - Fasano, Edvige
AU  - Fasano E
FAU - Matullo, Giuseppe
AU  - Matullo G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 11002-13-4 (Angiotensinogen)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiotensinogen/*genetics
MH  - Case-Control Studies
MH  - Female
MH  - Genotype
MH  - Glomerulonephritis, Membranous/*genetics/physiopathology
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Nitric Oxide Synthase/*genetics
MH  - Nitric Oxide Synthase Type III
MH  - Peptidyl-Dipeptidase A/*genetics
MH  - *Polymorphism, Genetic
MH  - Receptor, Angiotensin, Type 1/*genetics
EDAT- 2004/02/10 05:00
MHDA- 2004/07/14 05:00
CRDT- 2004/02/10 05:00
PHST- 2004/02/10 05:00 [pubmed]
PHST- 2004/07/14 05:00 [medline]
PHST- 2004/02/10 05:00 [entrez]
AID - 10.1093/ndt/gfg604 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2004 Mar;19(3):587-95. doi: 10.1093/ndt/gfg604.