ORIGINAL PAPER Coding region analysis of vitamin D receptor gene and its association with active calcium stone disease Abbas Basiri • Nasser Shakhssalim • Massoud Houshmand • Amir H. Kashi • Mohaddeseh Azadvari • Banafsheh Golestan • Esmaeel Mohammadi Pargoo • Hamid Pakmanesh Received: 7 February 2011 / Accepted: 23 June 2011 / Published online: 4 August 2011 Ó Springer-Verlag 2011 Abstract The purpose of this study was to evaluate the impact of vitamin D receptor (VDR) gene polymorphisms on the status of active renal calcium stone formation. Male active renal calcium stone formers (ASF, final N = 106) with two episodes of stone relapse in the past 5 years were enrolled from December 2008 to April 2009. Controls (N = 109) were selected from age range- and gender-mat- ched individuals who had no evidence or history of stone disease. Sequencing and single-strand conformational polymorphism were used to determine VDR polymorphisms in the patients and controls. Three polymorphisms were identified in the VDR gene: (1) start codon polymorphism (rs2228570T [ C; p.M1T); (2) C/T polymorphism in the second intron (NT-029419.12: g.10416049C [ T); (3) a silent polymorphism in exon 9 (rs731236T [ C; p.I352I). Start codon polymorphism was the only one that was associated with the status of calcium stone formation (p \ 0.05). We performed a complete coding genome analysis of VDR gene and observed that only start codon polymorphism was related to the status of active calcium stone formation. Keywords Vitamin D receptor Á Polymorphism Á Nephrolithiasis Á Etiology Á Calcium stone Introduction Familial aggregation of kidney stones has been reported since 1874 [4]. Several later epidemiologic studies have emphasized a genetic predisposition to kidney stones [6, 13, 18], which is the strongest risk factor after controlling for dietary factors [5, 18]. The mode of inheritance is thought to be polygenic [2, 18]. Vitamin D is an important hormone in calcium metab- olism, including intestinal calcium absorption and renal calcium resorption [7, 14]. Single nucleotide polymor- phism (SNP) is one way to map complex disease traits and has been used to investigate the relationship of vitamin D receptor (VDR) polymorphisms with different diseases [2]. Vitamin D is involved in calcium homeostasis, in immune system and cancer [8]. More than 60 polymorphisms have been reported in the VDR gene. Most of these polymor- phisms are in introns or regulatory areas other than exons A. Basiri Á N. Shakhssalim Á A. H. Kashi Á M. Azadvari Á H. Pakmanesh Urology and Nephrology Research Center (UNRC), Shahid Labbafinejad Medical Center, Shahid Beheshti University, M.C. (SBMU), Tehran, Islamic Republic of Iran N. Shakhssalim UNRC, Shahid Labbafinejad Medical Center, SBMU, Tehran, Islamic Republic of Iran M. Houshmand (&) Houshmand Medical Molecular Genetic Lab., Genetic Diagnostic Department, National Institute for Genetic Engineering and Biotechnology, Special Medical Center(Charity Foundation for Special Diseases), UNRC, No#103, Boostan 9th St., Pasdaran Ave., 1666677951 Tehran, Islamic Republic of Iran e-mail: massoud_houshmand@yahoo.com A. H. Kashi Á M. Azadvari Á H. Pakmanesh UNRC, SBMU, Tehran, Islamic Republic of Iran B. Golestan Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, UNRC, Tehran, Islamic Republic of Iran E. Mohammadi Pargoo Department of Biology, Faculty of Sciences Islamic Azad University, Science and Research Campus, Special Medical Center, Tehran, Islamic Republic of Iran 123 Urol Res (2012) 40:35–40 DOI 10.1007/s00240-011-0399-1