To the Editor:
We appreciate the interest1 in our report2 in which ANKH polymorphisms were not identified as major determinants of susceptibility to ankylosing spondylitis (AS) and do not influence phenotypic characteristics of AS — age at disease onset or results of the Bath AS Disease Activity Index, Bath AS Functional Index, or modified Stoke Ankylosing Spondylitis Spine Score2.
Occurrence of renal stones was not evaluated in our study of Portuguese patients with AS2. There are some data showing an increased prevalence of renal stone formation in patients with AS/spondyloarthritis3,4. Moreover it was described that the transmembrane protein ANKH is expressed in kidney tissues such as cilia and basal body structures, as well as epithelial cells5. Considering the function of ANKH as a pyrophosphate transporter and regulator of tissue calcification, a potential role in renal stone formation represents an interesting hypothesis for study. However, no association between ANKH and renal stone formation was seen in the study described by Korkmaz and Sayer1; it is important to mention that that study was clearly underpowered to elicit evidence for this kind of association.
Despite weak positive associations described by some authors6,7, there is convincing evidence that the ANKH gene has no significant role in AS2,8. In addition, no association was identified with this gene and AS susceptibility in large studies using high numbers of nonsynonymous SNP9 or in genome-wide association studies10.
There are several concerns regarding the studies focusing on ANKH variants: (1) methodological differences (ethnicity, case ascertainment approaches, and ANKH marker variants analyzed); and (2) all of them were underpowered to detect genes with small effects consistently. Thus further studies are needed to reach definitive conclusions.