NDT Advance Access originally published online on February 7, 2006
Nephrology Dialysis Transplantation 2006 21(4):1125; doi:10.1093/ndt/gfl014
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Reply
Email: Angela.Summers{at}cmmc.nhs.ukSir,
In response to the letter by Doi et al., we would like to highlight the differences between the populations that we and Doi et al. studied, which might explain the apparent discrepancies in the association of VEGF genetic polymorphisms with end-stage renal disease (ESRD).
Firstly, the ethnic origins are likely to be different. The authors do not state the ethnicity of their populations, either disease or control, but we assume that they are predominantly Japanese or Asian. In our publication, we clearly state that our population was predominantly Caucasian. Ethnicity is likely to be important in that polymorphism frequencies may be affected by racial origin. In a publication by Awata et al. [1], the authors report an association of VEGF polymorphisms with diabetic retinopathy in a Japanese population. They report that the frequencies of the –460C/T in type 2 diabetics are no different from their healthy controls. In contrast, the frequencies of the –460C/T are notably different from our healthy Caucasian controls. It is also of note that Doi et al. did not genotype directly for the –460C/T polymorphism and the information, with respect to the frequency of this polymorphism in their normal population and ESRD population, is not clearly presented for comparison. Previous studies investigating Single Nucleotide Polymorphism (SNP) distributions have demonstrated that there are major differences between racial groups [2–4].
Another important difference is that the frequencies of the cause of ESRD differ between the two studies. In our study, cohort 1 were all selected from a population with glomerulonephritis (GN). In cohort 2, 32% had GN, 18.5% had Adult Polycystic Kidney Disease (APKD), 4.1% were diabetic, 9.2% were diagnosed with obstructive uropathy and 8.2% had nephrosclerosis with 22% of unknown aetiology.
In the study by Doi et al. 48% had GN, 27% had diabetic nephropathy, 13% had nephrosclerosis and 12% had miscellaneous other conditions.
We suggest that these important differences between the two populations’ studies may explain the discrepancy.
Conflict of interest statement. None declared.
Manchester Institute of Nephrology and Transplantation Manchester Royal Infirmary Manchester UK
References
- Awata T, Inoue K, Kurihara S et al. A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 2002; 51: 1635–1639
[Abstract/Free Full Text] - Hassan MI, Aschner Y, Manning CH, Xu J, Aschner JL. Racial differences in selected cytokine allelic and genotypic frequencies among healthy, pregnant women in North Carolina. Cytokine 2003; 21: 10–16[CrossRef][Web of Science][Medline]
- Dvornyk V, Liu XH, Shen H et al. Differentiation of Caucasians and Chinese at bone mass candidate genes: implication for ethnic difference of bone mass. Ann Hum Genet 2003; 67: 216–227[Medline]
- Eisman JA. Genetics of osteoporosis. Endocr Rev 1999; 20: 788–804
[Abstract/Free Full Text]
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