Rutherford et al. (2001) report: (1) the association of a bi- allelic variant in the promoter of the inducible nitric oxide synthase gene (NOS2A) with hypertension, (2) the pres- ence of two loci for hypertension on chromosome 17, and (3) a lack of association for two other genes on this chro- mosome. Having been involved in this research, I must take issue with what is reported. Candidate gene study of NOS2A Rutherford et al. (2001) claim that a bi-allelic variant lo- cated in the promoter of NOS2A shows association with hypertension (although P= only 0.034), the minor allele frequency being 0.148 vs 0.087 for hypertensive vs nor- motensive groups. Most of the 121 patient samples used for this study (unrelated hypertensives with two hyperten- sive parents) were supplied by my laboratory, i.e., were largely from Sydney, which is in the state of New South Wales, Australia. This source is not disclosed in the paper and is a notable omission since the control group used by Rutherford et al. (2001) had been recruited (by others for a skin cancer trial) from the geographically remote, small rural town of Nambour located in the state of Queensland. Their study design is thus inappropriate, so putting in jeop- ardy any finding arising. Importantly, but not revealed in the Rutherford et al. (2001) paper, a similar association study for the NOS2A marker, using most of same patient samples, but with a more appropriate control group (from Sydney), has al- ready been published, and was negative (Glenn et al. 1999). Glenn et al. (1999) found allele frequencies of 0.14 in control and 0.13 in hypertensives aged <60 years (n=149 and 71, respectively). Moreover, the frequency found by Bellamy and Hill (1997), who first reported this polymorphism in a general white population in the UK, was 0.15 for the minor allele, which resembles the value obtained by Rutherford et al. (2001) for the patient group, not the control group. In referring to our study at the start of the final para- graph of their Discussion, Rutherford et al. (2001) state “a previously published study was able to show NOS2A in- volvement in a subsection of essential hypertensive indi- viduals above 60 years of age (Glenn et al. 1999)”. This misrepresents my laboratory’s conclusions, which were that there was no association of the NOS2A marker with hypertension. Moreover, genotype does not change with age, unless that genotype is having a deleterious effect to increase mortality, which was our interpretation of our data for the 38 older hypertensives. Others have also excluded involvement of Nos2 in ge- netically hypertensive rats (Deng 1998; Dukhanina et al. 1997; Rapp 2000), so offering additional lack of support for the finding by Rutherford et al. (2001). Linkage study This study involved 177 affected sibpairs from eastern Australia, most of whom were collected by my laboratory without attribution. The bench work for the chromosome 17 scan began in my laboratory and was continued by Rutherford et al. Data arising for 8 of the 13 markers was reported in abstract form in 1997 (Rutherford et al. 1997), showing a suggestive linkage for one marker. In the pre- sent paper, a single marker (D17S949) generated Lod scores (1.7–2.36) and P-values (0.0096–0.0025) that are suggestive of linkage with hypertension. Although sup- port from flanking markers was not reported, others have nevertheless found linkage of this general region of chro- mosome 17 with hypertension (Baima et al. 1999; Julier et al. 1997; Levy et al. 2000; Pan et al. 2000) and with the rare hypertensive disorder pseudohypoaldosteronism type II (Wilson et al. 2001). Rutherford et al. (2001) also report Brian J. Morris Critique of “Chromosome 17 and the inducible nitric oxide synthase gene in human essential hypertension” by Rutherford et al., Human Genetics, published online September 2001 Hum Genet (2002) 110 : 98–99 DOI 10.1007/s00439-001-0641-y Received: 1 October 2001 / Accepted: 5 October 2001 / Published online: 13 December 2001 LETTER TO THE EDITORS B.J. Morris (✉) Professor of Physiology, Basic & Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, Building F13, The University of Sydney, NSW 2006, Australia Tel.: +61-2-93513688, Fax: +61-2-93512227 © Springer-Verlag 2001