This Article Full Text Full Text (PDF) All Versions of this Article: 41/6/e11    most recent 01.HYP.0000069261.30233.CFv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Seccia, T. M. Articles by Tokunaga, K. Search for Related Content PubMed PubMed Citation Articles by Seccia, T. M. Articles by Tokunaga, K. Related Collections Other diabetes Genetics of cardiovascular disease Endothelium/vascular type/nitric oxide

(Hypertension. 2003;41:e11.)
© 2003 American Heart Association, Inc.

Letters to the Editor

Endothelial Nitric Oxide Synthase Gene Polymorphisms and Renal Survival

Department of Clinical Methodology and Medical-Surgical Technologies, University of Bari, Italy

Gian Paolo Rossi

Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Italy

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

Development of end stage renal disease (ESRD) and a blunted in vitro generation of nitric oxide (NO) have been recently associated with the 298Asp substitution in the endothelial NO synthase (eNOS) gene.¹ Diabetic nephropathy was the culprit of ESRD in most patients (pts);¹ however, the same association was recently reported in pts with ESRD due to polycystic kidney disease.² Collectively these results would imply that a 298Asp allele–determined predisposition to generate less NO is mechanistically related with decreased renal survival. If proven, this appealing hypothesis could open new avenues to pharmacological prevention of ESRD.

However, some caveats suggest caution in jumping to this conclusion. First, criteria for patient enrollment were not given, and therefore a selection bias cannot be excluded.¹ Second, both studies were small since each entailed less than 200 ESRD pts. Sample size calculation showed that even in the larger study¹ a two-group ² test with a 0.05 two-sided significance level had only 60% power to detect a Glu298Asp genotype frequency difference between ESRD pts and controls. Thus, these were either lucky or serendipitous findings. Under both circumstances larger studies are mandatory. Furthermore, eNOS allele frequency differs markedly between Japanese and Caucasians; thus, these results must be replicated in populations with different ethnic backgrounds. Third, the restriction fragment length polymorphism analysis (RFLP) used for genotyping¹ cannot be as accurate as it should be. We replaced this methodology with the melting curve analysis³ because of inconsistent amplicon cleavage with BanII resulting in misdiagnosis of GT and . . . [Full Text of this Article]

Eisei Noiri; Toshiro Fujita

Departments of Nephrology and Endocrinology

Katsushi Tokunaga

Department of Human Genetics, The University of Tokyo, Japan