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Titolo:
Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism
Autore:
Zanchi, A; Moczulski, DK; Hanna, LS; Wantman, M; Warram, JH; Krolewski, AS;
Indirizzi:
Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, Boston, MA 02215 USA Harvard Univ Boston MA USA 02215 Epidemiol,Div Res, Boston, MA 02215 USA Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA Harvard Univ BostonMA USA 02215 Sch Med, Dept Med, Boston, MA 02215 USA
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 2, volume: 57, anno: 2000,
pagine: 405 - 413
SICI:
0085-2538(200002)57:2<405:ROADNI>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
MISSENSE GLU298ASP VARIANT; ESSENTIAL-HYPERTENSION; LINKAGE ANALYSIS; MICROALBUMINURIA; MELLITUS; DYSFUNCTION; DISEASE; JAPANESE; IDDM; SUSCEPTIBILITY;
Keywords:
gene for NOS; IDDM; DNA sequence; eNOS polymorphism; diabetes; endothelium;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Krolewski, AS Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, 1 Joslin Pl,Room 305, Boston, MA 02215 USA Harvard Univ 1 Joslin Pl,Room 305 Boston MA USA 02215 15 USA
Citazione:
A. Zanchi et al., "Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism", KIDNEY INT, 57(2), 2000, pp. 405-413

Abstract

Background. Polymorphisms in the endothelial nitric oxide synthase gene (eNOS) may be implicated in the development of nephropathy in patients with type 1 or insulin-dependent diabetes mellitus (IDDM). Methods. Three groups of IDDM patients were selected to study this hypothesis: cases with advanced diabetic nephropathy (N = 78), cases with overt proteinuria but normal serum creatinine (N = 74), and controls with normoalbuminuria despite 15 years of diabetes (N = 195). Parents of 132 cases and 53controls were also examined and were used for the transmission disequilibrium test, a family-based study design to test association. Results. We examined four eNOS polymorphisms, and two were associated withdiabetic nephropathy in the case-control comparisons: a T to C substitution in the promoter at position -786 and the a-deletion/b-insertion in intron4. For the former, the risk of developing advanced nephropathy was higher for C allele homozygotes than for the other two genotypes (odds ratio 2.8, 95% CI, 1.4 to 5.6). For the latter polymorphism, it was the a-deletion carriers that had the higher risk (odds ratio 2.3, 95% CI, 1.3 to 4.0) in comparison with noncarriers. Both polymorphisms were analyzed together as haplotypes in a family-based study using the transmission disequilibrium test. The C/a-deletion haplotype was transmitted from heterozygous parents to cases with advanced diabetic nephropathy with a significantly higher frequency than expected (P = 0.004). Conclusion. The findings of the case-control and family-based studies demonstrate clearly that DNA sequence differences in eNOS influence the risk ofadvanced nephropathy in type 1 diabetes.

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Documento generato il 30/09/20 alle ore 09:10:47