BERKELEY, CA (UroToday.com) - In the past few years, we have been working to explore the possible gene single nucleotide polymorphisms (SNPs) as genetic makers for renal stone diseases.
Calcium oxalate urolithiasis is a multi-factorial disease. The majority are idiopathic, indicating the absence of any identifiable clinical cause of the disease. Besides environmental factors, genetic factors such as family history influence stone pathogenesis suggesting that genetic factors substantially influence the developing kidney stone diseases.
Genetic markers of stone disease could be useful for identifying patients at risk, and for preventing urolithiasis. Our serial reports have proposed some genes including vitamin D receptor, androgen- and oestrogen-receptor, calcitonin receptor, interleukin (IL)-1Î² and receptor antagonist, urokinase, vascular endothelial growth factor, and E-cadherin gene polymorphisms as candidates for genetic markers of stone diseases.
Inflammation may be one of causes of urolithiasis. IL-18 is a pro-inflammatory cytokine, initially isolated from liver, which shares structural features with IL-1Î². We demonstrated that IL-18 SNPs are associated with urolithiasis in our sample population, a subset of the Chinese population in Taiwan. The patients with allele C in IL-18 +105A/C and with a G/G homozygote in IL-18 -137G/C have a higher risk of developing urolithiasis. To date, only a few gene SNPs have been studied for their relationship to urolithiasis, and much of the genetic background of patients with urolithiasis still needs to be identified. Our positive results encourage us to seek other cytokine network genes for potential associations with kidney stone disease. Nevertheless, in addition of this candidate gene, it should take whole cytokines genes as a network to be studied in the further investigations.
Genome-wide association studies (GWAS) have recently proven a powerful strategy in identifying genetic contributors to complex traits. The field of human genetics is evolving rapidly, and recent modern technologies can help investigators make practical methodological choices for discovering new genetic variants that influence clinical traits or phenotypes.
Our report suggests an association between IL-18 SNPs and the risk of urolithiasis. We hope that the results of our investigation will contribute to the understanding of the pathogenic mechanisms of urolithiasis, and expand potential predictive markers for urolithiasis. In addition, new approaches in genetic research, such as GWAS, are necessary for the discovery of new genetic variants that influence in kidney stone diseases.
- Edvardsson VO, Palsson R, Indridason OS, et al. Familiality of kidney stone disease in Iceland. Scand J Urol Nephrol. 2009;43(5):420-424.
- Chen WC, Chen HY, Lu HF, et al. Association of the vitamin D receptor gene start codon Fok I polymorphism with calcium oxalate stone disease. BJU Int. 2001;87(3):168-171.
- Chen WC, Wu HC, Lin WC, et al. The association of androgen- and oestrogen-receptor gene polymorphisms with urolithiasis in men. BJU Int. 2001;88(4):432-436.
- Chen WC, Wu HC, Lu HF, et al. Calcitonin receptor gene polymorphism: a possible genetic marker for patients with calcium oxalate stones. Eur Urol. 2001;39(6):716-719.
- Chen WC, Wu HC, Chen HY, et al. Interleukin-1Î² gene and receptor antagonist gene polymorphisms in patients with calcium oxalate stones. Urol Res. 2001;29(5):321-324.
- Tsai FJ, Lin CC, Lu HF, et al. Urokinase gene 3â€™-UTR T/C polymorphism is associated with urolithiasis. Urology. 2002;59(3):458-461.
- Chen WC, Chen HY, Wu HC, et al. Vascular endothelial growth factor gene polymorphism is associated with calcium oxalate stone disease. Urol Res. 2003;31(3):218-222.
- Tsai FJ, Wu HC, Chen HY, et al. Association of E-cadherin gene 3â€™-UTR C/T polymorphism with calcium oxalate stone disease. Urol Int. 2003;70(4):278-281.
- Khan SR, Kok DJ. Modulators of urinary stone formation. Front Biosci. 2004;9:1450-1482.
- Lai KC, Lin WY, Man KM, et al. Association of interleukin-18 gene polymorphisms with calcium oxalate kidney stone disease. Scand J Urol Nephrol. 2010;44(1):20-26.
- Sale MM, Mychaleckyj JC, Chen WM. Planning and executing a genome wide association study (GWAS). Methods Mol Biol. 2009;590:403-418.
Yung-Hsiang Chen, PhD,a Huey-Yi Chen, MD, PhD,a,b and Wen-Chi Chen, MD, PhDa,c as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
- Department of Obstetric and Gynecology and
- Department of Urology, China Medical University and Hospital, Taichung, Taiwan.